igf type 1 receptor

Summary

Summary: A protein-tyrosine kinase receptor that is closely related in structure to the INSULIN RECEPTOR. Although commonly referred to as the IGF-I receptor, it binds both IGF-I and IGF-II with high affinity. It is comprised of a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precusor protein. The beta subunit contains an intrinsic tyrosine kinase domain.

Top Publications

  1. ncbi The role of the IGF system in cancer growth and metastasis: overview and recent insights
    Amir Abbas Samani
    Department of Medicine, McGill University Health Center, Royal Victoria Hospital, Room H6 25687, Pine Avenue West, Montreal, Quebec, Canada H3A 1A1
    Endocr Rev 28:20-47. 2007
  2. ncbi Hyperactivation of the insulin-like growth factor receptor I signaling pathway is an essential event for cisplatin resistance of ovarian cancer cells
    Niels Eckstein
    Center of Advanced European Studies and Research caesar, Bonn, Germany
    Cancer Res 69:2996-3003. 2009
  3. ncbi The insulin-like growth factor system and cancer
    Derek LeRoith
    Diabetes Branch, Room 8D12, Building 10, National Institutes of Health MSC 1758, Bethesda, MD 20892 1758, USA
    Cancer Lett 195:127-37. 2003
  4. ncbi Insulin-like growth factor-I receptor signaling and resistance to trastuzumab (Herceptin)
    Y Lu
    Department of Oncology, Jewish General Hospital, and McGill University, Montreal, PQ, Canada
    J Natl Cancer Inst 93:1852-7. 2001
  5. ncbi A recombinant humanized anti-insulin-like growth factor receptor type I antibody (h7C10) enhances the antitumor activity of vinorelbine and anti-epidermal growth factor receptor therapy against human cancer xenografts
    Liliane Goetsch
    Centre d Immunologie Pierre Fabre, 5 Avenue Napoleon III, 74160, St Julien en Genevois, France
    Int J Cancer 113:316-28. 2005
  6. ncbi IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice
    Martin Holzenberger
    Institut National de la Santé et de la Recherche Médicale U515, Hopital Saint Antoine, 75571 Paris 12, France
    Nature 421:182-7. 2003
  7. pmc Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial-mesenchymal transition
    Hanna Y Irie
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 171:1023-34. 2005
  8. ncbi Role of insulin-like growth factors in embryonic and postnatal growth
    J Baker
    Department of Genetics and Development, Columbia University, New York, New York 10032
    Cell 75:73-82. 1993
  9. ncbi Circulating insulin-like growth factor-I levels regulate colon cancer growth and metastasis
    Yiping Wu
    Section of Cellular and Molecular Physiology, Cellular Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892 1758, USA
    Cancer Res 62:1030-5. 2002
  10. ncbi Distinct and overlapping functions of insulin and IGF-I receptors
    J Nakae
    Naomi Berrie Diabetes Center, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    Endocr Rev 22:818-35. 2001

Detail Information

Publications305 found, 100 shown here

  1. ncbi The role of the IGF system in cancer growth and metastasis: overview and recent insights
    Amir Abbas Samani
    Department of Medicine, McGill University Health Center, Royal Victoria Hospital, Room H6 25687, Pine Avenue West, Montreal, Quebec, Canada H3A 1A1
    Endocr Rev 28:20-47. 2007
    ....
  2. ncbi Hyperactivation of the insulin-like growth factor receptor I signaling pathway is an essential event for cisplatin resistance of ovarian cancer cells
    Niels Eckstein
    Center of Advanced European Studies and Research caesar, Bonn, Germany
    Cancer Res 69:2996-3003. 2009
    ..We conclude that targeting the IGF-IR and the PI3K pathways is a promising new strategy to treat cisplatin-resistant ovarian carcinomas...
  3. ncbi The insulin-like growth factor system and cancer
    Derek LeRoith
    Diabetes Branch, Room 8D12, Building 10, National Institutes of Health MSC 1758, Bethesda, MD 20892 1758, USA
    Cancer Lett 195:127-37. 2003
    ..In this review, many aspects of the IGF system and its relationship to cancer will be discussed...
  4. ncbi Insulin-like growth factor-I receptor signaling and resistance to trastuzumab (Herceptin)
    Y Lu
    Department of Oncology, Jewish General Hospital, and McGill University, Montreal, PQ, Canada
    J Natl Cancer Inst 93:1852-7. 2001
    ..Thus, strategies that target IGF-IR signaling may prevent or delay development of resistance to trastuzumab...
  5. ncbi A recombinant humanized anti-insulin-like growth factor receptor type I antibody (h7C10) enhances the antitumor activity of vinorelbine and anti-epidermal growth factor receptor therapy against human cancer xenografts
    Liliane Goetsch
    Centre d Immunologie Pierre Fabre, 5 Avenue Napoleon III, 74160, St Julien en Genevois, France
    Int J Cancer 113:316-28. 2005
    ....
  6. ncbi IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice
    Martin Holzenberger
    Institut National de la Santé et de la Recherche Médicale U515, Hopital Saint Antoine, 75571 Paris 12, France
    Nature 421:182-7. 2003
    ..The Igf1r(+/-) mice display greater resistance to oxidative stress, a known determinant of ageing. These results indicate that the IGF-1 receptor may be a central regulator of mammalian lifespan...
  7. pmc Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial-mesenchymal transition
    Hanna Y Irie
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 171:1023-34. 2005
    ..These results highlight the distinct functions of Akt isoforms in regulating growth factor-stimulated EMT and cell migration, as well as the importance of Akt1 in cross-regulating the ERK signaling pathway...
  8. ncbi Role of insulin-like growth factors in embryonic and postnatal growth
    J Baker
    Department of Genetics and Development, Columbia University, New York, New York 10032
    Cell 75:73-82. 1993
    ....
  9. ncbi Circulating insulin-like growth factor-I levels regulate colon cancer growth and metastasis
    Yiping Wu
    Section of Cellular and Molecular Physiology, Cellular Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892 1758, USA
    Cancer Res 62:1030-5. 2002
    ..This study supports the hypothesis that circulating IGF-I levels play an important role in tumor development and metastasis...
  10. ncbi Distinct and overlapping functions of insulin and IGF-I receptors
    J Nakae
    Naomi Berrie Diabetes Center, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    Endocr Rev 22:818-35. 2001
    ..The phenotypes of insulin receptor gene mutations in humans and in mice indicate important differences between the developmental roles of insulin and its receptor in the two species...
  11. ncbi Cyclolignans as inhibitors of the insulin-like growth factor-1 receptor and malignant cell growth
    Ada Girnita
    Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Hospital, Stockholm, Sweden
    Cancer Res 64:236-42. 2004
    ..Our results open the possibility to use PPP or related compounds with inhibitory effects on IGF-1R as lead compounds in development of anticancer agents...
  12. ncbi The IGF-1 receptor in cancer biology
    Renato Baserga
    Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, 624 BLSB, Philadelphia, PA 19107, USA
    Int J Cancer 107:873-7. 2003
    ..Downregulation of the IGF-1R leads to massive apoptosis of cancer cells. These characteristics make it an attractive target for anticancer therapy...
  13. ncbi In vivo antitumor activity of NVP-AEW541-A novel, potent, and selective inhibitor of the IGF-IR kinase
    Carlos Garcia-Echeverria
    Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH 4002 Basel, Switzerland
    Cancer Cell 5:231-9. 2004
    ..Thus, NVP-AEW541 represents a class of selective, small molecule IGF-IR kinase inhibitors with proven in vivo antitumor activity and potential therapeutic application...
  14. ncbi Inhibition of the insulin-like growth factor receptor-1 tyrosine kinase activity as a therapeutic strategy for multiple myeloma, other hematologic malignancies, and solid tumors
    Constantine S Mitsiades
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Cancer Cell 5:221-30. 2004
    ....
  15. ncbi Structure and autoregulation of the insulin-like growth factor 1 receptor kinase
    S Favelyukis
    Department of Physiology and Biophysics, School of Medicine State University of New York at Stony Brook, Stony Brook, New York 11794, USA
    Nat Struct Biol 8:1058-63. 2001
    ..Although the nucleotide binding cleft is conserved between IGF1RK and the insulin receptor kinase, sequence differences in the nearby interlobe linker could potentially be exploited for anticancer drug design...
  16. ncbi Structural biology of insulin and IGF1 receptors: implications for drug design
    Pierre De Meyts
    Receptor Biology Laboratory, Hagedorn Research Institute, Niels Steensens Vej 6, DK 2820 Gentofte, Denmark
    Nat Rev Drug Discov 1:769-83. 2002
    ....
  17. pmc The Grb10/Nedd4 complex regulates ligand-induced ubiquitination and stability of the insulin-like growth factor I receptor
    Andrea Vecchione
    Department of Urology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Mol Cell Biol 23:3363-72. 2003
    ..This is the first demonstration of regulation of stability of a tyrosine kinase receptor by the Nedd4 (HECT) family of E3 ligases...
  18. ncbi Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r)
    J P Liu
    Department of Genetics and Development, Columbia University, New York, New York 10032
    Cell 75:59-72. 1993
    ..The roles of the IGFs in mouse embryonic development, as revealed from the phenotypic differences between these mutants, are discussed...
  19. pmc Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins
    Marta Guix
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 6307, USA
    J Clin Invest 118:2609-19. 2008
    ..Moreover, combined therapeutic inhibition of EGFR and IGFIR may abrogate this acquired mechanism of drug resistance and is thus worthy of prospective clinical investigation...
  20. ncbi Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor
    L E Smith
    Department of Ophthalmology, Harvard Medical School and Children s Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nat Med 5:1390-5. 1999
    ..They also explain why diabetic retinopathy initially increases with the onset of insulin treatment. IGF-1 levels, low in untreated diabetes, rise with insulin therapy, permitting VEGF-induced retinopathy...
  21. ncbi IGF-1 upregulates electroneutral K-Cl cotransporter KCC3 and KCC4 which are differentially required for breast cancer cell proliferation and invasiveness
    Yueh Mei Hsu
    Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan
    J Cell Physiol 210:626-36. 2007
    ..Thus, we conclude that KCC activation by IGF-1 plays an important role in IGF-1 receptor signaling to promote growth and spread of breast cancer cells...
  22. ncbi Aberrant expression and activation of insulin-like growth factor-1 receptor (IGF-1R) are mediated by an induction of IGF-1R promoter activity and stabilization of IGF-1R mRNA and contributes to growth factor independence and increased survival of the panc
    P N Nair
    Department of Surgery, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
    Oncogene 20:8203-14. 2001
    ..This likely protects cells from unfavorable conditions and allows cells to rapidly re-enter the cell cycle when conditions are favorable...
  23. ncbi Luteolin inhibits insulin-like growth factor 1 receptor signaling in prostate cancer cells
    Jing Fang
    The Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Graduate School of Chinese Academy of Sciences, Shanghai 200031, China
    Carcinogenesis 28:713-23. 2007
    ..Immunoblotting of the extracts of tumor tissues showed that luteolin inhibited IGF-1R/AKT signaling. Our results provide a new insight into the mechanisms that luteolin is against cancer cells...
  24. ncbi Role of IGF system of mitogens in the induction of fibroblast proliferation by keloid-derived keratinocytes in vitro
    Toan Thang Phan
    National Burns Centre, Singapore General Hospital, Singapore 169608
    Am J Physiol Cell Physiol 284:C860-9. 2003
    ....
  25. ncbi daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans
    K D Kimura
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Science 277:942-6. 1997
    ..Life-span regulation by insulin-like metabolic control is analogous to mammalian longevity enhancement induced by caloric restriction, suggesting a general link between metabolism, diapause, and longevity...
  26. pmc Mdm2-dependent ubiquitination and degradation of the insulin-like growth factor 1 receptor
    Leonard Girnita
    Department of Oncology and Pathology, Division of Cellular and Molecular Tumor Pathology, Cancer Center Karolinska, R8 04, Karolinska Hospital, SE 171 76 Stockholm, Sweden
    Proc Natl Acad Sci U S A 100:8247-52. 2003
    ..Consequently, by sequestering Mdm2 in the cell nuclei, the level of p53 may indirectly influence the expression of IGF-1R. This role of Mdm2 and p53 represents an unexpected mechanism for the regulation of IGF-1R and cell growth...
  27. ncbi Insulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositide 3-kinase signaling
    Arnab Chakravarti
    Department of Radiation Oncology, Massachusetts General Hospital Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Cancer Res 62:200-7. 2002
    ..These findings suggest that IGFR-I signaling through phosphoinositide 3-kinase may represent a novel and potentially important mechanism of resistance to anti-EGFR therapy...
  28. pmc Igf1r as a therapeutic target in a mouse model of basal-like breast cancer
    Apostolos Klinakis
    Department of Genetics and Development, Columbia University, 1150 St Nicholas Avenue, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 106:2359-64. 2009
    ..PPP also was effective against xenografts of the human basal-like cancer cell line MDA-MB-231, which carries a KRAS(G13D) mutation...
  29. ncbi Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use
    P Kurtzhals
    Health Care Discovery, Novo Nordisk, Bagsvaerd, Denmark
    Diabetes 49:999-1005. 2000
    ..The reduced in vitro potency of insulin detemir might explain why this analog is not as effective on a molar basis as human insulin in humans...
  30. ncbi Insulin-like growth factor type-I receptor internalization and recycling mediate the sustained phosphorylation of Akt
    Robert J Romanelli
    Department of Neurology and Neurosciences, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA
    J Biol Chem 282:22513-24. 2007
    ..Mathematical modeling of receptor trafficking further supports these results and predicts an additional kinetic state of the receptor consistent with sustained Akt phosphorylation...
  31. ncbi Signalling by the type 1 insulin-like growth factor receptor: interplay with the epidermal growth factor receptor
    Timothy E Adams
    CSIRO Health Sciences and Nutrition, 343 Royal Parade, Parkville, VIC 3052, Australia
    Growth Factors 22:89-95. 2004
    ..This review describes the components of the IGF signalling system and gives an overview of the emerging picture of the interrelationship that is now known to exist between the IGF and EGF receptors...
  32. ncbi Combination therapy enhances the inhibition of tumor growth with the fully human anti-type 1 insulin-like growth factor receptor monoclonal antibody CP-751,871
    Bruce D Cohen
    Pfizer Global Research and Development, Inc, Eastern Point Road, Groton, CT 06340, USA
    Clin Cancer Res 11:2063-73. 2005
    ..We generated and characterized a human monoclonal antibody that targeted the IGF receptor...
  33. ncbi Down-regulation of type I insulin-like growth factor receptor increases sensitivity of breast cancer cells to insulin
    Hua Zhang
    University of Minnesota Cancer Center, 420 Delaware Street Southeast, Minneapolis, MN 55455, USA
    Cancer Res 67:391-7. 2007
    ..Because IR also activates signaling pathways similar to IGF1R in breast cancer cells, agents targeting both receptors may be necessary to disrupt the malignant phenotype regulated by this growth factor system...
  34. ncbi In vivo effects of the human type I insulin-like growth factor receptor antibody A12 on androgen-dependent and androgen-independent xenograft human prostate tumors
    Jennifer D Wu
    Department of Medicine, University of Washington, Seattle, Washington 98104, USA
    Clin Cancer Res 11:3065-74. 2005
    ..In this study, we tested the in vivo effects of A12 on androgen-dependent and androgen-independent prostate tumor growth...
  35. ncbi {beta}-Arrestin is crucial for ubiquitination and down-regulation of the insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 ligase
    Leonard Girnita
    Department of Oncology and Pathology, Division of Cellular and Molecular Tumor Pathology, Cancer Center Karolinska, R8 04, Karolinska Hospital, SE 171 76 Stockholm, Sweden
    J Biol Chem 280:24412-9. 2005
    ..To our knowledge this is the first study demonstrating a defined molecular role of beta-arrestin with direct relevance to cell growth and cancer...
  36. ncbi Ataxia-telangiectasia mutated gene controls insulin-like growth factor I receptor gene expression in a deoxyribonucleic acid damage response pathway via mechanisms involving zinc-finger transcription factors Sp1 and WT1
    Limor Shahrabani-Gargir
    Department of Clinical Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Endocrinology 145:5679-87. 2004
    ..Deregulated expression of the IGF-IR gene after ionizing radiation may be linked to genomic instability and enhanced transforming capacity...
  37. pmc Wild-type and mutant p53 differentially regulate transcription of the insulin-like growth factor I receptor gene
    H Werner
    Section on Molecular and Cellular Physiology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 93:8318-23. 1996
    ..Mutant versions of p53 protein, usually associated with malignant states, can derepress the IGF-I-R promoter, with ensuing mitogenic activation by locally produced or circulating IGFs...
  38. ncbi Regulation of breast cancer cell motility by insulin receptor substrate-2 (IRS-2) in metastatic variants of human breast cancer cell lines
    J G Jackson
    Department of Medicine, Division of Medical Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, TX 78229, USA
    Oncogene 20:7318-25. 2001
    ..In these cells, IGF-I enhances cell adhesion and motility suggesting that IRS-2 may mediate these aspects of the malignant phenotype...
  39. ncbi Overexpression of the insulin-like growth factor I receptor in human colon carcinomas
    Matthias M Weber
    Klinik II und Poliklinik für Innere Medizin der Universität zu Köln und Lehrstuhl II für Innere Medizin, Koln, Germany
    Cancer 95:2086-95. 2002
    ..However, definitive studies of IGF-IR expression in these tissues have not been performed...
  40. ncbi Insulin-like growth factor-I receptor/human epidermal growth factor receptor 2 heterodimerization contributes to trastuzumab resistance of breast cancer cells
    Rita Nahta
    Department of Breast Medical Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030 4009, USA
    Cancer Res 65:11118-28. 2005
    ....
  41. ncbi Inhibition of the type I insulin-like growth factor receptor expression and signaling: novel strategies for antimetastatic therapy
    P Brodt
    Department of Surgery, McGill University Health Center, Montreal, Quebec, Canada
    Biochem Pharmacol 60:1101-7. 2000
    ....
  42. ncbi Blockade of insulin-like growth factor I receptor function inhibits growth and angiogenesis of colon cancer
    Niels Reinmuth
    Departments of Cancer Biology, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 8:3259-69. 2002
    ..To elucidate the in vitro and in vivo effects of IGF-IR in human colon cancer growth and angiogenesis, HT29 cells were transfected with a truncated dominant-negative (DN) form of IGF-IR or vector alone...
  43. ncbi Insulin-like growth factor-I stimulated DNA replication in mouse endometrial stromal cells
    Ayako Inoue
    Department of Biology, Faculty of Science, Okayama University, Japan
    J Reprod Dev 51:305-13. 2005
    ..These results suggest that endometrial IGF-I is involved in the proliferation of endometrial stromal cells in a paracrine or autocrine manner, and that the MAP kinase pathway is involved in DNA replication of endometrial stromal cells...
  44. ncbi High coexpression of both insulin-like growth factor receptor-1 (IGFR-1) and epidermal growth factor receptor (EGFR) is associated with shorter disease-free survival in resected non-small-cell lung cancer patients
    V Ludovini
    Division of Medical Oncology, Public Hospital, Perugia, Italy
    Ann Oncol 20:842-9. 2009
    ..We explored the correlation between IGFR-1 and EGFR, their relationship with clinicopathological parameters and their impact on outcome in resected stage I-III NSCLC patients...
  45. ncbi Crystal structure of bisphosphorylated IGF-1 receptor kinase: insight into domain movements upon kinase activation
    A Pautsch
    Boehringer Ingelheim Pharma KG Deutschland, Birkendorferstrasse 65, D 88400 Biberach, Germany
    Structure 9:955-65. 2001
    ..Structures of the homologous insulin receptor kinase (IRK) exist in an open, unphosphorylated form and a closed, trisphosphorylated form...
  46. ncbi Insulin-like growth factor-I receptor as a marker for prognosis and a therapeutic target in human esophageal squamous cell carcinoma
    Arisa Imsumran
    First Department of Internal Medicine, Sapporo Medical University, South 1, West 16, Chuo Ku, Sapporo 060 8543, Japan
    Carcinogenesis 28:947-56. 2007
    ..Therapeutic blockade of IGF-Ir may be a useful anticancer therapeutic for ESCC...
  47. ncbi Regulation of apoptosis by insulin-like growth factor (IGF)-I
    Ron Kooijman
    Department of Pharmacology, Free University of Brussels VUB, Laarbeeklaan 103, B 1090 Brussels, Belgium
    Cytokine Growth Factor Rev 17:305-23. 2006
    ..This phenomenon may explain the efficacy of IGF-I as an inhibitor of apoptosis in many different cell types and in the presence of different apoptogenic stimuli...
  48. ncbi IMC-A12, a human IgG1 monoclonal antibody to the insulin-like growth factor I receptor
    Eric K Rowinsky
    Department of Clinical Research and Regulatory Affairs, ImClone Systems Incorporated, Branchburg, New Jersey 08876, USA
    Clin Cancer Res 13:5549s-5555s. 2007
    ..The results with IMC-A12 to date suggest that it may be an effective therapeutic in a diverse array of oncologic indications...
  49. pmc Functionally significant insulin-like growth factor I receptor mutations in centenarians
    Yousin Suh
    Departments of Medicine and Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 105:3438-42. 2008
    ..Thus, genetic alterations in the human IGF1R that result in altered IGF signaling pathway confer an increase in susceptibility to human longevity, suggesting a role of this pathway in modulation of human lifespan...
  50. ncbi The insulin-like growth factor-I receptor as a target for cancer therapy
    Renato Baserga
    Thomas Jefferson University, Kimmel Cancer Center, 233 S 10th Street, 624 BLSB, Philadelphia, PA 19107, USA
    Expert Opin Ther Targets 9:753-68. 2005
    ..This review focuses on the mechanisms underlying the experimental findings, and discusses the possibility of extrapolating the results obtained in animals to the cure of human tumours...
  51. ncbi Src phosphorylates the insulin-like growth factor type I receptor on the autophosphorylation sites. Requirement for transformation by src
    J E Peterson
    Department of Microbiology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA
    J Biol Chem 271:31562-71. 1996
    ..Thus, the Src kinase can substitute for the receptor kinase in phosphorylating and activating the IGF-I receptor, and this receptor phosphorylation and activation are essential for transformation by src...
  52. ncbi Inhibition of insulin-like growth factor-I receptor (IGF-IR) signaling and tumor cell growth by a fully human neutralizing anti-IGF-IR antibody
    Yan Wang
    Department of Oncology, Schering Plough Research Institute, 2015 Galloping Hill Road, K15 4600, Kenilworth, NJ 07033, USA
    Mol Cancer Ther 4:1214-21. 2005
    ..In vivo, 19D12 inhibits the tumor growth of a very aggressive human ovarian tumor xenograft model A2780. These data support the development of this anti-IGF-IR monoclonal antibody as a promising anticancer agent...
  53. ncbi Tumor development by transgenic expression of a constitutively active insulin-like growth factor I receptor
    Joan M Carboni
    Oncology Drug Discovery and Discovery Toxicology, Bristol Myers Squibb Research Institute, Princeton, New Jersey 08534, USA
    Cancer Res 65:3781-7. 2005
    ..This new model should provide new opportunities for further understanding how aberrant IGF-IR signaling leads to tumorigenesis and for optimizing novel antagonists of the receptor kinase...
  54. pmc Insulin receptor substrates mediate distinct biological responses to insulin-like growth factor receptor activation in breast cancer cells
    S A Byron
    Department of Pharmacology, University of Minnesota Cancer Center, Minneapolis, MN 55455, USA
    Br J Cancer 95:1220-8. 2006
    ..As multiple agents targeting the IGF-IR are currently in early clinical trials, IRS expression should be considered as a potential biomarker for IGF-IR responsiveness...
  55. ncbi IGF-I increases IGFBP-5 and collagen alpha1(I) mRNAs by the MAPK pathway in rat intestinal smooth muscle cells
    Xiping Xin
    Univ of Michigan Medical School, Rm 6520 MSRB I, 1150 West Medical Center Dr, Ann Arbor, MI 48109 0682, USA
    Am J Physiol Gastrointest Liver Physiol 286:G777-83. 2004
    ..These results suggest that the MAPK pathway is key to IGF-I-mediated gene regulation in intestinal smooth muscle cells, whereas data do not suggest a role for the Akt-dependent pathway in our system...
  56. ncbi Differential insulin-like growth factor I receptor signaling and function in estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 breast cancer cells
    M Bartucci
    Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Cancer Res 61:6747-54. 2001
    ..Our results suggest that in breast cancer cells, IGF-IR can control nonmitogenic processes regardless of the ER status, whereas IGF-IR growth-related functions may depend on ER expression...
  57. ncbi Function of the IGF-I receptor in breast cancer
    E Surmacz
    Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Mammary Gland Biol Neoplasia 5:95-105. 2000
    ..Consequently, IGF-IR function in the late stages of breast cancer remains one of the most important questions to be addressed before rational anti-IGF-IR therapies are developed...
  58. ncbi Regulation of the insulin-like growth factor-I receptor gene by oncogenes and antioncogenes: implications in human cancer
    H Werner
    Department of Clinical Biochemistry, Tel Aviv University, Tel Aviv, 69978, Israel
    Mol Genet Metab 71:315-20. 2000
    ..Interactions between stimulatory and inhibitory transcription factors may determine the level of expression of the IGF-I-R gene and, consequently, the proliferative status of the cell...
  59. ncbi Placental glycogen stores are increased in mice with H19 null mutations but not in those with insulin or IGF type 1 receptor mutations
    Diego R Esquiliano
    Endocrine Division, Children s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Placenta 30:693-9. 2009
    ..Results obtained from insulin receptor or IGF Type 1 receptor mutant mice did not show differences in placental glycogen content compared to their wild-type littermates, ..
  60. ncbi The insulin-like growth factor-I (IGF-I) receptor kinase inhibitor NVP-ADW742, in combination with STI571, delineates a spectrum of dependence of small cell lung cancer on IGF-I and stem cell factor signaling
    G Sakuntala Warshamana-Greene
    Department of Medicine, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia 23249, USA
    Mol Cancer Ther 3:527-35. 2004
    ..These observations suggest that, in tumors in which critical signal transduction pathways can be activated by alternative receptors, optimal therapy may require inhibition of multiple receptors...
  61. ncbi Insulin-like growth factor I receptor pathway inhibition by ADW742, alone or in combination with imatinib, doxorubicin, or vincristine, is a novel therapeutic approach in Ewing tumor
    Ana S Martins
    Laboratory 20 Molecular Pathology, Centro de Investigación del Cáncer Instituto de Biología Molecular y Celular del Cáncer, Universidad de Salamanca Consejo Superior de Investigaciones Cientificas, Salamanca, Spain
    Clin Cancer Res 12:3532-40. 2006
    ..We recently showed the cytostatic role of imatinib, an inhibitor of the SCF-KIT loop, on Ewing tumor cells, and in this study, we intend to analyze the inhibition of the insulin-like growth factor I receptor (IGF1R) loop...
  62. ncbi Osteoblast-specific knockout of the insulin-like growth factor (IGF) receptor gene reveals an essential role of IGF signaling in bone matrix mineralization
    Mei Zhang
    Department of Medicine, University of Cincinnati, Ohio 45267, USA
    J Biol Chem 277:44005-12. 2002
    ..This action is likely to be particularly important during the pubertal growth spurt when rapid bone formation and consolidation are required...
  63. ncbi Insulin-like growth factor-1 receptor in uveal melanoma: a predictor for metastatic disease and a potential therapeutic target
    Charlotta All-Ericsson
    St Erik s Eye Hospital, Stockholm, Sweden
    Invest Ophthalmol Vis Sci 43:1-8. 2002
    ..To investigate the expression of the insulin-like growth factor-1 receptor (IGF-1R) with special focus on its role in cell growth in uveal melanoma...
  64. ncbi Insulin-like growth factor receptor I targeting in epithelial ovarian cancer
    Walter H Gotlieb
    Division of Gynecologic Oncology, McGill University, Montreal, Quebec, Canada
    Gynecol Oncol 100:389-96. 2006
    ..Preclinical evaluation of the anti-neoplastic activity of an insulin-like growth factor I receptor (IGF-IR) kinase inhibitor in ovarian cancer...
  65. pmc Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization
    Tatsuya Kondo
    Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Clin Invest 111:1835-42. 2003
    ..These data indicate that both insulin and IGF-1 signaling in endothelium play a role in retinal neovascularization through the expression of vascular mediators, with the effect of insulin being most important in this process...
  66. ncbi The cyclolignan PPP induces activation loop-specific inhibition of tyrosine phosphorylation of the insulin-like growth factor-1 receptor. Link to the phosphatidyl inositol-3 kinase/Akt apoptotic pathway
    Daiana Vasilcanu
    Department of Oncology and Pathology, Division of Cellular and Molecular Tumor Pathology, CCK, R8 04, Karolinska Hospital, SE 17176 Stockholm, Sweden
    Oncogene 23:7854-62. 2004
    ..PPP was proven not to interfere directly with Akt or any of its downstream molecules in the apoptotic pathway...
  67. ncbi Combined in vivo effect of A12, a type 1 insulin-like growth factor receptor antibody, and docetaxel against prostate cancer tumors
    Jennifer D Wu
    Department of Medicine, University of Washington, Seattle, WA 98104, USA
    Clin Cancer Res 12:6153-60. 2006
    ..Based on these data, we investigated the combined in vivo effect of A12 and docetaxel on human androgen-independent and osseous prostate tumor growth...
  68. ncbi Insulin-like growth factor type 1 receptor expression correlates to good prognosis in highly malignant soft tissue sarcoma
    Jan Ahlén
    Department of Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
    Clin Cancer Res 11:206-16. 2005
    ..To evaluate known and suggested prognostic markers, especially insulin-like growth factor type 1 receptor (IGF-1R), in highly malignant soft tissue sarcomas (STS)...
  69. ncbi The insulin-like growth factor-I receptor kinase inhibitor, NVP-ADW742, sensitizes small cell lung cancer cell lines to the effects of chemotherapy
    G Sakuntala Warshamana-Greene
    Department of Medicine, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, VA 23249, USA
    Clin Cancer Res 11:1563-71. 2005
    ..The purpose of this study was to determine whether the novel IGF-I receptor (IGF-IR) kinase inhibitor, NVP-ADW742, sensitizes SCLC cell lines to etoposide and carboplatin, which are commonly used in the treatment of SCLC...
  70. ncbi Lipid rafts/caveolae are essential for insulin-like growth factor-1 receptor signaling during 3T3-L1 preadipocyte differentiation induction
    Hairong Huo
    State Laboratory of Molecular Biology and Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
    J Biol Chem 278:11561-9. 2003
    ....
  71. ncbi Localization of insulin-like growth factor-I in lung tissues of patients with fibroproliferative acute respiratory distress syndrome
    Peter M Krein
    Department of Medicine, University of Calgary, Health Sciences Center, Calgary, Alberta, Canada
    Am J Respir Crit Care Med 167:83-90. 2003
    ..Our results indicate that IGF-I is increased in FP-ARDS and may be an important mediator in the progression of acute lung injury to FP-ARDS...
  72. ncbi Re-expression of estrogen receptor alpha in estrogen receptor alpha-negative MCF-7 cells restores both estrogen and insulin-like growth factor-mediated signaling and growth
    S Oesterreich
    Breast Center, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
    Cancer Res 61:5771-7. 2001
    ..These data show that ERalpha is a critical requirement for IGF signaling, and to our knowledge this is the first report of functional ERalpha expression that confers estrogen-mediated growth of an ER-negative breast cancer cell line...
  73. ncbi Association of insulin-like growth factor 1 receptor with EHD1 and SNAP29
    R Rotem-Yehudar
    Department of Cell Research and Immunology, Tel Aviv University, Ramat Aviv, 69978, Tel Aviv, Israel
    J Biol Chem 276:33054-60. 2001
    ....
  74. ncbi Crosstalk between the insulin-like growth factors and estrogens in breast cancer
    D Yee
    Department of Medicine, University of Minnesota Cancer Center, Minneapolis 55455, USA
    J Mammary Gland Biol Neoplasia 5:107-15. 2000
    ..Taken together, these observations suggest that the two growth regulatory pathways are tightly linked and that a further understanding of the mechanism of this crosstalk could lead to new therapeutic strategies in breast cancer...
  75. ncbi Inhibition of in vivo breast cancer growth by antisense oligodeoxynucleotides to type I insulin-like growth factor receptor mRNA involves inactivation of ErbBs, PI-3K/Akt and p42/p44 MAPK signaling pathways but not modulation of progesterone receptor acti
    Mariana Salatino
    Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental IBYME, CONICET, Obligado 2490, Buenos Aires 1428, Argentina
    Oncogene 23:5161-74. 2004
    ..Our results for the first time demonstrated that breast cancer growth can be inhibited by direct in vivo administration of IGF-IR AS[S]ODNs...
  76. ncbi Structure and function of the type 1 insulin-like growth factor receptor
    T E Adams
    CSIRO Health Sciences and Nutrition, Parkville, Victoria, Australia
    Cell Mol Life Sci 57:1050-93. 2000
    ..Recent progress towards the elucidation of the three-dimensional structure of the extracellular domain of the IGF-1R represents an opportunity for the rational assembly of small molecule antagonists of receptor function for clinical use...
  77. ncbi Growth-promoting interaction of IGF-II with the insulin receptor during mouse embryonic development
    A Louvi
    Department of Genetics and Development, Columbia University, New York, New York, 10032, USA
    Dev Biol 189:33-48. 1997
    ..Therefore, these results provide genetic evidence that the growth-promoting function of IGF-II during mouse embryogenesis is mediated in part by signaling through the insulin receptor...
  78. ncbi Down-regulation of IGF-IR using small, interfering, hairpin RNA (siRNA) inhibits growth of human lung cancer cell line A549 in vitro and in nude mice
    Ai qiang Dong
    Department of Cardiothoracic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, P R China
    Cell Biol Int 31:500-7. 2007
    ..Our results support the therapeutic potential of RNAi as a method for gene therapy in treating lung cancer...
  79. ncbi Insulin-like growth factor-I receptor signalling and acquired resistance to gefitinib (ZD1839; Iressa) in human breast and prostate cancer cells
    H E Jones
    Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Redwood Building, University of Cardiff, King Edward VII Avenue, Cardiff CF10 3XF, UK
    Endocr Relat Cancer 11:793-814. 2004
    ....
  80. ncbi A pivotal role for heat shock protein 90 in Ewing sarcoma resistance to anti-insulin-like growth factor 1 receptor treatment: in vitro and in vivo study
    Ana Sofia Martins
    Laboratory 20 Molecular Pathology, Centro de Investigación del Cáncer Instituto de Biología Molecular y Celular del Cáncer, Universidad de Salamanca Consejo Superior de Investigaciones Cientificas, Salamanca, Spain
    Cancer Res 68:6260-70. 2008
    ..Accordingly, HSP90 expression could be a predictive factor of response to IGF1R-targeting therapies...
  81. ncbi The insulin-like growth factor 1 receptor induces physiological heart growth via the phosphoinositide 3-kinase(p110alpha) pathway
    Julie R McMullen
    Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 279:4782-93. 2004
    ..This study suggests that targeting the cardiac IGF1R-PI3K(p110alpha) pathway could be a potential therapeutic strategy for the treatment of heart failure...
  82. ncbi Characterization of the insulin-like growth factor axis in a human hepatoma cell line (PLC)
    J G Scharf
    Department of Medicine, George August Universität, Gottingen, Germany
    Carcinogenesis 19:2121-8. 1998
    ..The present data point to the IGF axis as a complex regulatory system that self limits the mitogenic activity of exogenous IGFs...
  83. ncbi PBK/TOPK promotes tumour cell proliferation through p38 MAPK activity and regulation of the DNA damage response
    V Ayllon
    Cell Biology Laboratory, Department of Biochemistry, Biosciences Institute, National University of Ireland, Cork, Ireland
    Oncogene 26:3451-61. 2007
    ..Thus, enhanced expression of PBK may facilitate tumour growth by mediating p38 activation and by helping cells to overcome DNA damage...
  84. pmc 14-3-3 proteins interact with the insulin-like growth factor receptor but not the insulin receptor
    R W Furlanetto
    Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Biochem J 327:765-71. 1997
    ..Our findings suggest that 14-3-3 proteins may play a role in IGFIR signal transduction and may contribute to the differences in IGF and IR signalling capabilities...
  85. ncbi The insulin-like growth factor-I receptor inhibitor picropodophyllin causes tumor regression and attenuates mechanisms involved in invasion of uveal melanoma cells
    Ada Girnita
    Cellular and Molecular Tumor Pathology, Department of Oncology and Pathology, Cancer Centre Karolinska R8 04, Karolinska Hospital, Stockholm, Sweden
    Clin Cancer Res 12:1383-91. 2006
    ..Therefore, new molecular targets important for malignant phenotype of uveal melanoma have to be found to design efficient pharmacologic agents...
  86. pmc Addiction to elevated insulin-like growth factor I receptor and initial modulation of the AKT pathway define the responsiveness of rhabdomyosarcoma to the targeting antibody
    Liang Cao
    Genetics Branch, Center for Cancer Research, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892 4265, USA
    Cancer Res 68:8039-48. 2008
    ..Subsequent progression of tumors was associated with reactivation of p-AKT despite sustained suppression of IGF-IR. These results identified the first predictive biomarker for anti-IGF-IR therapies in cancer...
  87. ncbi Evidence for a differential interaction of SHC and the insulin receptor substrate-1 (IRS-1) with the insulin-like growth factor-I (IGF-I) receptor in the yeast two-hybrid system
    S Tartare-Deckert
    INSERM U145, Nice, France
    J Biol Chem 270:23456-60. 1995
    ..Finally, our data highlight the crucial role of the juxtamembrane domain in signaling by both the IR and the IGF-IR...
  88. ncbi Development of new insulin-like growth factor-1 receptor kinase inhibitors using catechol mimics
    Galia Blum
    Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel
    J Biol Chem 278:40442-54. 2003
    ..The ability to replace catechol groups with a moiety that is more stable in cells may aid in developing non-catechol-containing substrate-competitive inhibitors targeted toward IGF-1R and possibly against other protein-tyrosine kinases...
  89. ncbi Insulin-like growth factors in human breast cancer
    M J Ellis
    Lombardi Cancer Center, Georgetown University, Washington, DC 20007, USA
    Breast Cancer Res Treat 52:175-84. 1998
    ....
  90. ncbi Modifying IGF1 activity: an approach to treat endocrine disorders, atherosclerosis and cancer
    David R Clemmons
    Division of Endocrinology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599 7170, USA
    Nat Rev Drug Discov 6:821-33. 2007
    ..Therefore, inhibiting IGF1 action has been proposed as a specific mechanism for potentiating the effects of existing anticancer therapies or for directly inhibiting tumour cell growth...
  91. ncbi A dominant negative type I insulin-like growth factor receptor inhibits metastasis of human cancer cells
    Deepali Sachdev
    Department of Medicine and Cancer Center, University of Minnesota, Minnesota 55455, USA
    J Biol Chem 279:5017-24. 2004
    ..Our data show that IGF1R can regulate several aspects of the malignant phenotype. In these cells, metastasis but not proliferation requires IGF1R function...
  92. ncbi IGF1R signalling and its inhibition
    J Riedemann
    Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, Oxford OX3 9DS, UK
    Endocr Relat Cancer 13:S33-43. 2006
    ..It will be important to use data from preclinical and early clinical trials to establish the molecular correlates of sensitivity to IGF1R blockade, and the optimum means of combining this new approach with standard treatment modalities...
  93. ncbi Normal values of circulating insulin-like growth factor-I bioactivity in the healthy population: comparison with five widely used IGF-I immunoassays
    Michael P Brugts
    Department of Internal Medicine, Erasmus MC, Dr Molewaterplein 50, Rotterdam, The Netherlands
    J Clin Endocrinol Metab 93:2539-45. 2008
    ..Recently an IGF-I-specific kinase receptor activation assay (KIRA) has been developed as an alternative method. However, no normative values have been established for the IGF-I KIRA...
  94. ncbi Insulin-like growth factor 1 receptor activates c-SRC and modifies transformation and motility of colon cancer in vitro
    Madhavi Sekharam
    Department of Interdisciplinary Oncology, Moffitt Cancer Center and Research Institute, University of South Florida, 12902 Magnolia Drive, Tampa, FL 33612 9497, USA
    Anticancer Res 23:1517-24. 2003
    ..Based on the above observations, we conclude that an overexpressed and activated IGF1-R may increase the degree of transformation and motility of colon cancer cells by activating c-Src...
  95. ncbi Insulin analogues with increased mitogenic potency--are they safe?
    B F Hansen
    Diabetes Biology, Novo Nordisk A S, Måløv, Denmark
    Horm Metab Res 40:431-3. 2008
  96. ncbi IGF type 1 receptor ligand binding characteristics are altered in a subgroup of children with intrauterine growth retardation
    B Ducos
    Laboratoire d'Explorations Fonctionnelles Endocriniennes, , , and INSERM, U-515, , 75571 Paris, France
    J Clin Endocrinol Metab 86:5516-24. 2001
    ..Our results suggest heterogeneous alterations in IGF-IR binding function in IUGR patients...
  97. pmc Type I insulin-like growth factor receptor gene expression in normal human breast tissue treated with oestrogen and progesterone
    R B Clarke
    Clinical Research Department, Christie Hospital NHS Trust, Withington, Manchester, UK
    Br J Cancer 75:251-7. 1997
    ..The results are consistent with the suggestion that E2 may act to stimulate proliferation indirectly via a paracrine mechanism involving IGFs in normal as well as malignant human breast epithelial cells...
  98. ncbi Impaired Shc, Ras, and MAPK activation but normal Akt activation in FL5.12 cells expressing an insulin-like growth factor I receptor mutated at tyrosines 1250 and 1251
    Madeline Leahy
    Cell Biology Laboratory, Department of Biochemistry, Biosciences Institute, National University of Ireland, Cork, Ireland
    J Biol Chem 279:18306-13. 2004
    ..12 cells expressing this mutant and may also explain why this mutant IGF-IR is deficient in functions associated with cellular transformation and cell migration in fibroblasts and epithelial tumor cells...
  99. ncbi Insulin-like growth factor-1 (IGF-1) and IGF-1 receptor (IGF-1R) expression in human lung in RDS and BPD
    Anne Chetty
    Division of Pulmonology, Department of Pediatrics, Floating Hospital for Children, Tufts New England Medical Center, Boston, Massachusetts, USA
    Pediatr Pulmonol 37:128-36. 2004
    ..IGF-1 and IGF-R expression is low during fetal development, but is acutely upregulated in RDS, and persists with further upregulation in BPD...
  100. ncbi p53 regulates insulin-like growth factor-I (IGF-I) receptor expression and IGF-I-induced tyrosine phosphorylation in an osteosarcoma cell line: interaction between p53 and Sp1
    C Ohlsson
    Diabetes Branch, National Institute of Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 1770, USA
    Endocrinology 139:1101-7. 1998
    ..These data indicate that the IGF-I receptor is a physiological target for p53 in osteosarcoma cells. Furthermore, data supporting an interaction between p53 and Sp1 in the regulation of the promoter activity of IGF-IR are presented...
  101. ncbi The IGF-I receptor in mitogenesis and transformation of mouse embryo cells: role of receptor number
    M Rubini
    Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Exp Cell Res 230:284-92. 1997
    ..These experiments indicate that a small increment in the number of receptors per cell, well within the physiological range, can modulate the mitogenic and transforming activities of the IGF-IR in 3T3-like cells...

Research Grants67

  1. Response to and signals of caloric restriction and intermittent feeding regimens
    MARC KOPEL HELLERSTEIN; Fiscal Year: 2010
    ....
  2. Insulin Signaling and the Heart in Diabetes
    EVAN DALE ABEL; Fiscal Year: 2011
    ..Moreover, elucidation of the signaling mechanisms that regulate autophagy in cardiomyocytes may lead to novel therapies for preventing or modulating heart injury as occurs in diabetes, cardiac ischemia or cardiac hypertrophy. ..
  3. Adiposity and Outcomes of Clinically Localized Prostate Cancer
    Vincent L Freeman; Fiscal Year: 2013
    ..It will also shed light on ways to prevent prostate cancer recurrence that may involve new or existing medicines or lifestyle changes. ..
  4. INSULIN RECEPTOR STRUCTURE AND TURNOVER
    C Ronald Kahn; Fiscal Year: 2013
    ....
  5. IGF-1, Gender, Heart Failure and Longevity: A Paradigm Shift
    Piero Anversa; Fiscal Year: 2010
    ..Thus, the genetic-molecular status of the heart may condition the outcome of aging and genetic manipulations may interfere with the development of the cardiac senescent phenotype in both genders. ..
  6. Akt/mTOR Signaling in Energy Balance Modulation of Epithelial Carcinogenesis
    Stephen D Hursting; Fiscal Year: 2013
    ..Furthermore, the proposed studies will establish molecular mechanisms underlying the anticancer effects of CR, especially in the putative target cells (i.e., stem cells) for cancer development. ..
  7. The Insulin/IGF-I Axis in Diabetic Osteopathy
    John L Fowlkes; Fiscal Year: 2013
    ..Together, these studies will provide critical mechanistic and pre-clinical information needed to better understand how corrections in insulin and/or IGF-I in diabetes may be beneficial in preventing and treating diabetic osteopathy. ..
  8. ENaC Transport in Insulin Resistance: Role of Insulin &IGF-1 Receptors
    Vivek Bhalla; Fiscal Year: 2013
    ....
  9. Novel Strategy for Lung Cancer Treatment Using IGF-1R Inhibitor
    Ho Young Lee; Fiscal Year: 2013
    ..abstract_text> ..
  10. Insulin and IGF-1 regulation of the GnR H neuron
    Sara A DiVall; Fiscal Year: 2012
    ..These studies will provide insight into how the brain's control of reproduction is affected by the nutrition dependent hormones insulin and insulin-like growth factor-1. ..
  11. Short-term estradiol use in middle-age: implications for female cognitive aging
    Jill M Daniel; Fiscal Year: 2013
    ....
  12. Insulin-Like Growth Factor-1 and Atherosclerosis
    Patrice Delafontaine; Fiscal Year: 2013
    ..These findings should allow development of innovative therapies targeted at reducing acute vascular events that are most often related to plaque instability. ..
  13. Rapamycin-induced Selective Apoptosis in Malignant Cells
    Peter J Houghton; Fiscal Year: 2012
    ..The studies have the potential to radically alter outcome for these children, and reduce the debilitating sequellae of high dose radiation and chemotherapy. ..
  14. Novel multivalent/multifunctional agents derived from a humanized anti-insulin-li
    Thomas M Cardillo; Fiscal Year: 2010
    ....
  15. SMOOTH MUSCLE CELL PROLIFERATION IN HUMAN CORONARY ARTERY BYPASS GRAFTS
    Devendra K Agrawal; Fiscal Year: 2012
    ..The information obtained from this study should provide an opportunity to formulate superior therapeutic approaches. ..
  16. Molecularly guided multimodal theranostics for breast cancer
    Amit Joshi; Fiscal Year: 2013
    ..In addition, a preclinical study will be conducted to demonstrate early stage detection of pancreatic cancer in an orthotopic animal model with a molecularly targeting antibody-nanoshell-fluorescent dye based agent. ..
  17. Mechanisms of Age-Related Skeletal Resistance to BMP-7 and IGF-I
    John C Lee; Fiscal Year: 2012
    ..The goal of the current study is to provide a molecular basis for the development of novel therapeutic agents that will treat age related osteoporosis by activating signal transduction pathways used by bone anabolic agents. ..
  18. DYSREGULATION OF GLUCOSE HOMEOSTASIS IN AGING
    NIR J BARZILAI; Fiscal Year: 2013
    ..Here we suggest that strategies designed to tip the balance of IGF-1 action from peripheral to brain may maximize the good effects of IGF-1 while minimizing the bad effects of IGF-1 on cancer risk, leading to healthy life-span. ..
  19. IRS-1 and -2 signaling in mammary development and cancer
    Adrian V Lee; Fiscal Year: 2013
    ..The study will elucidate IRS function, and then translate this into human breast cancer to test if they affect patient prognosis and predict response to anti-IGF-IR inhibitors. ..
  20. Aging and IGF-1 Receptor in a three dimensional matrix
    Itay Bentov; Fiscal Year: 2013
    ..This is significant because understanding the basis of age-associated delayed wound healing could potentially offer novel therapeutic modalities. ..
  21. Mechanisms of photocarcinogenesis in geriatric skin
    Jeffrey B Travers; Fiscal Year: 2013
    ..Furthermore, we will continue to evaluate the utility of prophylactic therapies that can prevent the occurrence of aging-associated photocarcinogenesis. ..
  22. Peripheral and central IGF-1 action in energy balance and longevity modulation
    DEREK MAJOR HUFFMAN; Fiscal Year: 2012
    ....
  23. The role of central IGF- 1 feedback in the regulation of growth and metabolism
    CHRISTOPHER JOSEPH ROMERO; Fiscal Year: 2013
    ..These studies, moreover, will improve our understanding of the physiology of both normal and abnormal growth and the role of growth factors in regulating metabolism. ..
  24. PROTEIN NUTRITION IN EXPERIMENTAL UREMIA
    WILLIAM EVANS MITCH; Fiscal Year: 2013
    ..The significance of our results is that the two-hit model could apply to many conditions because GC and decreased insulin responses are present in many catabolic illnesses, ..
  25. Mechanisms for Increased Breast Cancer Risk in Type 2 Diabetes
    Derek LeRoith; Fiscal Year: 2013
    ....
  26. Insulin Resistance and Breast Cancer Prognosis in Black &White Women
    Derek LeRoith; Fiscal Year: 2013
    ..Samples of breast cancer tissue removed during primary surgical resection will be examined using immunohistochemistry to assess the role of insulin, insulin-like disparities in breast cancer prognosis between racial groups. ..
  27. Role of autophagy and lipid metabolism in organismal aging
    Malene Hansen; Fiscal Year: 2013
    ....
  28. Effects of insulin-like signaling, aging, and ubiquinone on C. elegans muscle
    Alfred L Fisher; Fiscal Year: 2013
    ..Together our project can provide insights into the roles of mitochondrial dysfunction in muscle during aging or in response to impaired ubiquinone synthesis due to medications such as statins. ..
  29. TYROSINE PHOSPHORYLATION AND GROWTH HORMONE SIGNALING
    Stuart J Frank; Fiscal Year: 2013
    ..These insights have potential relevance to the endocrinology of growth and the behavior of human cancers. ..
  30. The effects of PTEN on tyrosine kinase signaling in breast cancer
    Todd W Miller; Fiscal Year: 2011
    ..This information will guide the design, development, and application of targeted cancer therapies. ..
  31. The effects of PTEN on tyrosine kinase signaling in breast cancer
    Todd W Miller; Fiscal Year: 2013
    ..abstract_text> ..
  32. The Interaction of Thyroid Hormone and Wnt Signaling Pathways in the Growth Plate
    ROBERT TRACY BALLOCK; Fiscal Year: 2010
    ....
  33. The Impact of IRS2-microtubule interactions in the progression of breast cancer
    JOSE RAUL MERCADO-MATOS; Fiscal Year: 2013
    ..Additionally, our results can provide the rationale for the development of novel therapeutic approaches for the treatment of IRS2-dependent malignancies. ..
  34. Insulin networks in aging and obesity
    ASHLYN DIXON RITTER; Fiscal Year: 2013
    ..abstract_text> ..
  35. Telomeric Shortening, p53 and miR-34a Condition Senescence of Cardiac Progenitors
    Annarosa Leri; Fiscal Year: 2013
    ..We will focus on the interaction between p53, miR-34 and miR-34 target genes;miR-34 is a downstream effector of p53 and is proposed to be an important determinant of CPC and cardiac aging. ..
  36. IGF-II and Insulin Receptors in Neural Stem Cells
    Teresa L Wood; Fiscal Year: 2013
    ..Whereas both IGF-II and IGF-I activate the IGF type 1 receptor (IGF-1R), IGF-II also binds to a splice variant isoform of the insulin receptor (IR-A) supporting distinct ..
  37. Regulation of Muscle Autophagy and Mitophagy by Insulin and IGF-1 Signaling
    BRIAN TIMOTHY O'NEILL; Fiscal Year: 2013
    ..This study will elucidate the roles of insulin resistance, altered IGF-1 signaling and diabetes on muscle protein metabolism and hopefully identify therapeutic targets to both decrease muscle atrophy and enhance mitochondrial function. ..
  38. MOLECULAR BASIS OF CELL GROWTH CONTROL BY THE TOR KINASE
    Joseph Avruch; Fiscal Year: 2011
    ..The results of these studies will provide basis for therapeutic interventions in this pathway, which is crucial to both human cancers and to diseases like Type 2 diabetes ..
  39. TAS:: 75 0850 ::TAS RECOVERY ACT - ACTNOW CLINICAL TRIAL 8461
    David P Kelsen; Fiscal Year: 2009
    ....
  40. Peripheral and central IGF-1 action in energy balance and longevity modulation
    DEREK MAJOR HUFFMAN; Fiscal Year: 2013
    ..At the conclusion of the K99/R00 award, the candidate expects to have achieved his short-term and long-term career goals and to have elucidated novel and significant mechanisms relevant to IGF- 1 action and aging. ..
  41. TBC1D3: A HOMINOID-SPECIFIC GENE THAT REGULATES GROWTH FACTOR RECEPTOR SIGNALING
    Philip D Stahl; Fiscal Year: 2010
    ..TBC1D3 may serve as a model for developing an understanding of the function of human-specific genes in regulating complex signaling pathways. ..
  42. Mechanisms of Herceptin resistance
    Rita Nahta; Fiscal Year: 2013
    ..Understanding the mechanisms leading to acquired Herceptin resistance will ultimately lead to refined therapeutic strategies and improved survival rates for patients with breast cancer. ..
  43. Annexin A2 as a mediator of pancreatic cancer metastases
    Lei Zheng; Fiscal Year: 2013
    ..This in turn, will provide new targets against which to develop novel interventions that disrupt the communication, and in doing so, abrogate tumor progression and metastases. ..
  44. ETHANOL PLACENTO TOXICITY--INSULIN AND IGF-1 SIGNALLING
    Stanley Fisher; Fiscal Year: 1999
    ..The findings should also contribute to the general understanding of the mechanisms by which ethanol affects the biology of many human tissues, including those of the fetus. ..
  45. Tyrosine Phosphyorylation and Growth Hormone Signaling
    STUART FRANK; Fiscal Year: 2005
    ..These studies will significantly expand knowledge of GH and cytokine signaling and of biologicallyrelevant crosstalk between cytokine and growth factor signaling systems. ..
  46. Leptin modulation of insulin action in the islet b-cell
    Rohit Kulkarni; Fiscal Year: 2005
    ..abstract_text> ..
  47. IGF INDUCED TOXICITY IN PREIMPLANTATION EMBRYOS
    Kelle Moley; Fiscal Year: 2003
    ..Results of this work are expected to have a significant impact on reproductive endocrinology by providing scientific evidence to support new clinical interventions in patients with polycystic ovary syndrome. ..
  48. Growth Hormone, IGF-1 and Age-related Pathogenesis
    William Sonntag; Fiscal Year: 2003
    ..In addition, the results will provide important information on the potential risks of administration of growth hormone and IGF-l to the elderly. ..
  49. IGF INDUCED TOXICITY IN PREIMPLANTATION EMBRYOS
    Kelle Moley; Fiscal Year: 2007
    ..Thus, these studies are ultimately expected to have a great impact on the field of reproductive biology. [unreadable] [unreadable]..
  50. Physiologic Role of the Somatotroph IGF-1 Receptor
    Christopher Romero; Fiscal Year: 2009
    ..In the future, this may provide the basis for guidelines for the evaluation and treatment of children with growth disorders. ..
  51. Insulin-like Growth Factors & Esophageal Adenocarcinoma
    Thomas Vaughan; Fiscal Year: 2003
    ..abstract_text> ..
  52. Using BRET to measure insulin resistance and receptor cross-talk
    CHRISTOPHER HUPFELD; Fiscal Year: 2007
    ..This proposal uses a novel technology, bioluminescence resonance energy transfer, to study insulin resistance in real time in live cultured cells. [unreadable] [unreadable]..
  53. Hormonal signals, genome integrity and longevity
    Jan Vijg; Fiscal Year: 2009
    ..This will provide basic insight into genome deterioration in somatic cells and its possible contribution to the efferent pathways by which insulin signaling accelerates aging. ..
  54. IGF-1 APOPTOTIC DEFENSES IN MELANOCYTES AND VITILIGO
    Joseph Morelli; Fiscal Year: 2002
    ..abstract_text> ..
  55. PC1 IN INSULIN RESISTANT HUMANS
    Ira Goldfine; Fiscal Year: 2000
    ..Finally, the PI and collaborators will address whether interventions to improve insulin sensitivity in vivo (weight reduction and exercise) alter PC-1 expression and tyrosine kinase activity in humans. ..
  56. Insulin-like Growth Factor Receptor Antagonists
    DANIEL MONTICELLO; Fiscal Year: 2007
    ..In this fashion, the ligand will bind to the receptor, block binding by the authentic ligand, and lock the receptor in the inactive form. [unreadable] [unreadable] [unreadable]..
  57. DAUs as IGF-1 Receptor Inhibitors in Breast Cancer
    Jack F Youngren; Fiscal Year: 2010
    ..other kinases, and characterize the biological effects of altering the specificity of DAUs for the IGF-1 R. Together these studies will result in the production of well-characterized DAU-based compounds for anti-cancer drug development. ..
  58. ROLE OF IGFS IN WILMS TUMOR DEVELOPMENT
    JAMES PERDUE; Fiscal Year: 1991
    ....
  59. TRANSFORMING DOMAINS IN THE IGF-1 RECEPTOR
    Christian Sell; Fiscal Year: 1999
    ..The ability of these mutant receptors to induce entry into S phase, mitosis and various aspects of transformation; i.e. foci formation, anchorage independent growth, and tumorigenicity, will be determined. ..
  60. HYPERANDROGENISM AND INSULIN RESISTANCE IN WOMEN
    ROBERT BARBIERI; Fiscal Year: 1991
    ..These experiments should yield important information concerning the role of metabolic factors in the regulation of ovarian androgen production and metabolism...
  61. MODULATION OF RETINAL FUNCTION BY IGF-1
    Richard Kramer; Fiscal Year: 2001
    ..abstract_text> ..
  62. Dopamine, Tryosine, and their Metabolites in Aging in Neurodegenerative Disease
    Alfred Fisher; Fiscal Year: 2009
    ....
  63. Dissecting the Death Pathway in the Islet beta-cell
    Nika Danial; Fiscal Year: 2005
    ..abstract_text> ..
  64. Receptor 'transactivation' in insulin signaling.
    Louis Luttrell; Fiscal Year: 2004
    ..Understanding these mechanisms may lead to pharmacologic approaches to dissociate the potentially harmful proliferative effects of insulin family receptors from their anti-apoptotic and metabolic effects. ..
  65. Cytosolic Phospholipase A2 in Cardiac Hypertrophy
    Thomas Force; Fiscal Year: 2005
    ..abstract_text> ..
  66. Insulin-like Growth Factor 1 Vaccine for Cancer Prevention
    VICTOR RASO; Fiscal Year: 2009
    ..The cancer preventive action of these vaccines will be tested in several spontaneous tumor mouse strains. ..
  67. ETHANOL EFFECT ON CELL GROWTH
    Raphael Rubin; Fiscal Year: 1999
    ..The results will highlight the mechanisms by which ethanol interferes with the IGF system, and the consequent disruption of cell proliferation, and may provide a basis for more extensive studies of protective measures. ..