TSC1

Summary

Gene Symbol: TSC1
Description: tuberous sclerosis 1
Alias: LAM, TSC, hamartin, tuberous sclerosis 1 protein, tumor suppressor
Species: human

Top Publications

  1. pmc Oncogenes and tumor-suppressor genes
    T A Lehman
    Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892
    Environ Health Perspect 93:133-44. 1991
  2. ncbi Overlapping neurologic and cognitive phenotypes in patients with TSC1 or TSC2 mutations
    F E Jansen
    Rudolf Magnus Institute of Neuroscience, Department of Child Neurology, University Medical Centre, 3508 GA Utrecht, The Netherlands
    Neurology 70:908-15. 2008
  3. pmc Quantitative phosphorylation profiling of the ERK/p90 ribosomal S6 kinase-signaling cassette and its targets, the tuberous sclerosis tumor suppressors
    Bryan A Ballif
    Department of Cell Biology and Taplin Biological Mass Spectrometry Facility, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:667-72. 2005
  4. ncbi Mutation spectrum of the 9q34 tuberous sclerosis gene TSC1 in transitional cell carcinoma of the bladder
    Margaret A Knowles
    Division of Cancer Medicine Research, Cancer Research UK Clinical Centre, St James s University Hospital, Beckett Street, Leeds, West Yorkshire LS9 7TF, U K
    Cancer Res 63:7652-6. 2003
  5. pmc Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling
    Ken Inoki
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Genes Dev 17:1829-34. 2003
  6. pmc Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling
    Andrew R Tee
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:13571-6. 2002
  7. ncbi IKK beta suppression of TSC1 links inflammation and tumor angiogenesis via the mTOR pathway
    Dung Fang Lee
    Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cell 130:440-55. 2007
  8. pmc Redox regulates mammalian target of rapamycin complex 1 (mTORC1) activity by modulating the TSC1/TSC2-Rheb GTPase pathway
    Sei Yoshida
    Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 286:32651-60. 2011
  9. ncbi The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination
    G Benvenuto
    Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland, MD 20892, USA
    Oncogene 19:6306-16. 2000
  10. ncbi Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis
    Li Ma
    Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cell 121:179-93. 2005

Detail Information

Publications252 found, 100 shown here

  1. pmc Oncogenes and tumor-suppressor genes
    T A Lehman
    Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892
    Environ Health Perspect 93:133-44. 1991
    ..The mechanistic role of the known tumor-suppressor genes Rb-1 and p53 in the development of human lung carcinomas is being investigated in this epithelial cell model of human bronchogenic carcinogenesis...
  2. ncbi Overlapping neurologic and cognitive phenotypes in patients with TSC1 or TSC2 mutations
    F E Jansen
    Rudolf Magnus Institute of Neuroscience, Department of Child Neurology, University Medical Centre, 3508 GA Utrecht, The Netherlands
    Neurology 70:908-15. 2008
    The purpose of this study was to systematically analyze the associations between different TSC1 and TSC2 mutations and the neurologic and cognitive phenotype in patients with tuberous sclerosis complex (TSC).
  3. pmc Quantitative phosphorylation profiling of the ERK/p90 ribosomal S6 kinase-signaling cassette and its targets, the tuberous sclerosis tumor suppressors
    Bryan A Ballif
    Department of Cell Biology and Taplin Biological Mass Spectrometry Facility, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:667-72. 2005
    ..in the ERK/p90 ribosomal S6 kinase-signaling targets, the tuberous sclerosis complex (TSC) tumor suppressors TSC1 and TSC2...
  4. ncbi Mutation spectrum of the 9q34 tuberous sclerosis gene TSC1 in transitional cell carcinoma of the bladder
    Margaret A Knowles
    Division of Cancer Medicine Research, Cancer Research UK Clinical Centre, St James s University Hospital, Beckett Street, Leeds, West Yorkshire LS9 7TF, U K
    Cancer Res 63:7652-6. 2003
    ..However, during a search for candidate bladder tumor suppressor genes within the 9q34 region of LOH, we previously found a small number of mutations of TSC1, raising the ..
  5. pmc Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling
    Ken Inoki
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Genes Dev 17:1829-34. 2003
    Tuberous sclerosis complex (TSC) is a genetic disease caused by mutation in either TSC1 or TSC2. The TSC1 and TSC2 gene products form a functional complex and inhibit phosphorylation of S6K and 4EBP1...
  6. pmc Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling
    Andrew R Tee
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:13571-6. 2002
    ..These findings strongly implicate the tuberin-hamartin tumor suppressor complex as an inhibitor of mTOR and suggest that the formation of tumors within TSC patients may result from ..
  7. ncbi IKK beta suppression of TSC1 links inflammation and tumor angiogenesis via the mTOR pathway
    Dung Fang Lee
    Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cell 130:440-55. 2007
    ..The tuberous sclerosis 1 (TSC1)/TSC2 tumor suppressor complex serves as a repressor of the mTOR pathway, and disruption of TSC1/TSC2 complex function may ..
  8. pmc Redox regulates mammalian target of rapamycin complex 1 (mTORC1) activity by modulating the TSC1/TSC2-Rheb GTPase pathway
    Sei Yoshida
    Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 286:32651-60. 2011
    ..of the cellular redox potential with a cysteine oxidant or reducing agent failed to alter mTORC1 activity in TSC1(-/-) or TSC2(-/-) mouse embryonic fibroblast cells...
  9. ncbi The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination
    G Benvenuto
    Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland, MD 20892, USA
    Oncogene 19:6306-16. 2000
    We report here that overexpression of the tuberous sclerosis-1 (TSC1) gene product hamartin results in the inhibition of growth, as well as changes in cell morphology...
  10. ncbi Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis
    Li Ma
    Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cell 121:179-93. 2005
    Tuberous sclerosis (TSC) is a tumor syndrome caused by mutation in TSC1 or TSC2 genes. TSC tumorigenesis is not always accompanied by loss of heterozygosity (LOH)...
  11. ncbi TSC1 stabilizes TSC2 by inhibiting the interaction between TSC2 and the HERC1 ubiquitin ligase
    Huira Chong-Kopera
    Life Sciences Institute, Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 281:8313-6. 2006
    ..The TSC1 and TSC2 proteins, also called hamartin and tuberin, respectively, have been shown to regulate cell growth through inhibition of the mammalian target of ..
  12. pmc Bile acid exposure up-regulates tuberous sclerosis complex 1/mammalian target of rapamycin pathway in Barrett's-associated esophageal adenocarcinoma
    Chia Jui Yen
    Department of Molecular and Cellular Oncology, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Cancer Res 68:2632-40. 2008
    ..inflammation-associated signaling pathway involving I kappaB kinases beta (IKK beta), tuberous sclerosis complex 1 (TSC1), and mammalian target of rapamycin (mTOR) downstream effector S6 kinase (S6K1) was confirmed to be activated in ..
  13. pmc Abnormal growth of smooth muscle-like cells in lymphangioleiomyomatosis: Role for tumor suppressor TSC2
    Elena A Goncharova
    Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania, 421 Curie Boulevard, BRB II III, Philadelphia, PA 19104 6160, USA
    Am J Respir Cell Mol Biol 34:561-72. 2006
    The TSC1 and TSC2 proteins, which function as a TSC1/TSC2 tumor suppressor complex, are associated with lymphangioleiomyomatosis (LAM), a genetic disorder characterized by the abnormal growth of smooth muscle-like cells in the lungs...
  14. pmc Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis
    Umut Ozcan
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Harvard University, Boston, MA 02115, USA
    Mol Cell 29:541-51. 2008
    ..Loss of the tuberous sclerosis complex genes (TSC1 or TSC2) leads to constitutive activation of mTOR and downstream signaling elements, resulting in the development ..
  15. ncbi Pathogenesis of tuberous sclerosis subependymal giant cell astrocytomas: biallelic inactivation of TSC1 or TSC2 leads to mTOR activation
    Jennifer A Chan
    Division of Neuropathology, Department of Pathology, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Neuropathol Exp Neurol 63:1236-42. 2004
    ..of biallelic mutation of TSC1 or TSC2, suggesting that SEGAs develop due to complete loss of a functional tuberin-hamartin complex...
  16. doi Tuberous sclerosis complex: disease modifiers and treatments
    Kit Sing Au
    Division of Medical Genetics, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, Texas, USA
    Curr Opin Pediatr 20:628-33. 2008
    ..The two causative genes, TSC1 and TSC2, which code for hamartin and tuberin respectively, play central roles in regulating cell survival and proliferation signaling pathways...
  17. ncbi Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States
    Kit Sing Au
    Department of Pediatrics, The University of Texas Medical School at Houston, 77030, USA
    Genet Med 9:88-100. 2007
    ..We identified mutations in 72% (199/257) of de novo and 77% (53/68) of familial cases, with 17% of mutations in the TSC1 gene and 50% in the TSC2 gene. There were 4% unclassified variants and 29% with no mutation identified...
  18. ncbi Identification of 54 large deletions/duplications in TSC1 and TSC2 using MLPA, and genotype-phenotype correlations
    Piotr Kozlowski
    Genetics Laboratory, Division of Translational Medicine, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Hum Genet 121:389-400. 2007
    Tuberous sclerosis (TSC) is an autosomal dominant disorder caused by mutations in either of two genes, TSC1 and TSC2. Point mutations and small indels account for most TSC1 and TSC2 mutations...
  19. ncbi Hamartin and tuberin interaction with the G2/M cyclin-dependent kinase CDK1 and its regulatory cyclins A and B
    M G Catania
    Department of Pathology and Laboratory Medicine UCLA Medical Center, Los Angeles, California 90095 1732, USA
    J Neuropathol Exp Neurol 60:711-23. 2001
    ..TSC is associated with mutations in 2 genes, TSC1 and TSC2, which encode hamartin and tuberin, respectively. The functions of these proteins have yet to be determined...
  20. ncbi Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting: genotype--phenotype correlations and comparison of diagnostic DNA techniques in Tuberous Sclerosis Complex
    Ozgur Sancak
    Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands
    Eur J Hum Genet 13:731-41. 2005
    ..TSC is caused by mutations in either the TSC1 or TSC2 gene...
  21. ncbi Analysis of both TSC1 and TSC2 for germline mutations in 126 unrelated patients with tuberous sclerosis
    Y Niida
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Hum Mutat 14:412-22. 1999
    ..With the cloning of two causative genes, TSC1 and TSC2 it is now possible to analyze both genes in TSC patients and identify germline mutations...
  22. ncbi Multicompartmental distribution of the tuberous sclerosis gene products, hamartin and tuberin
    Yuji Yamamoto
    Department of Surgery, University of Washington, 1959 NE Pacific St, Box 356410, Seattle, WA 98195, USA
    Arch Biochem Biophys 404:210-7. 2002
    ..The function of the gene products, hamartin and tuberin, is not well understood but we have previously suggested a role in vesicular transport...
  23. ncbi Molecular genetic and phenotypic analysis reveals differences between TSC1 and TSC2 associated familial and sporadic tuberous sclerosis
    A C Jones
    Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, CF4 4XN, UK
    Hum Mol Genet 6:2155-61. 1997
    ..3 whilst the TSC1 gene, predicted to encode a novel protein termed hamartin, has recently been cloned from 9q34...
  24. ncbi Cell cycle-regulated phosphorylation of hamartin, the product of the tuberous sclerosis complex 1 gene, by cyclin-dependent kinase 1/cyclin B
    Aristotelis Astrinidis
    Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Biol Chem 278:51372-9. 2003
    Tuberous sclerosis complex is a tumor suppressor gene syndrome whose manifestations can include seizures, mental retardation, and benign tumors of the brain, skin, heart, and kidneys...
  25. ncbi Aspects of tuberous sclerosis complex (TSC) protein function in the brain
    V Ramesh
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Building 149, 13th Street, Charlestown, MA 02129, USA
    Biochem Soc Trans 31:579-83. 2003
    ..We have shown that hamartin interacts with neurofilament light chain (NF-L) and could integrate the neuronal cytoskeleton through its direct ..
  26. pmc Bladder tumour-derived somatic TSC1 missense mutations cause loss of function via distinct mechanisms
    Louis S Pymar
    Cancer Research UK Clinical Centre in Leeds, Leeds Institute for Molecular Medicine, St James s University Hospital, Beckett Street, Leeds LS9 7TF, UK
    Hum Mol Genet 17:2006-17. 2008
    More than 50% of transitional cell carcinomas of the bladder show loss of heterozygosity of a region spanning the TSC1 locus at 9q34 and mutations of TSC1 have been identified in 14.5% of tumours...
  27. pmc Mutational spectrum of the TSC1 gene in a cohort of 225 tuberous sclerosis complex patients: no evidence for genotype-phenotype correlation
    M van Slegtenhorst
    MGC Department of Clinical Genetics, Erasmus University, Rotterdam, The Netherlands
    J Med Genet 36:285-9. 1999
    Tuberous sclerosis complex is an inherited tumour suppressor syndrome, caused by a mutation in either the TSC1 or TSC2 gene...
  28. pmc Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity
    Yong Li
    Life Sciences Institute, Department of Biological Chemistry, University of Michigan, Ann Arbor 48109 0606, USA
    Mol Cell Biol 24:7965-75. 2004
    Tuberous sclerosis complex (TSC) is a genetic disease caused by a mutation in either the tsc1 or tsc2 tumor suppressor gene...
  29. pmc Missense mutations to the TSC1 gene cause tuberous sclerosis complex
    Mark Nellist
    Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands
    Eur J Hum Genet 17:319-28. 2009
    ..The disease is caused by mutations in either the TSC1 gene on chromosome 9q34 or the TSC2 gene on chromosome 16p13.3...
  30. ncbi Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles
    T L Plank
    Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Cancer Res 58:4766-70. 1998
    Tuberous sclerosis is an inherited syndrome associated with mutations in two tumor suppressor genes: TSC1 and TSC2...
  31. ncbi Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34
    M van Slegtenhorst
    Department of Clinical Genetics, Erasmus University and University Hospital, Rotterdam, Netherlands
    Science 277:805-8. 1997
    ..In one of these six, a somatic mutation in the wild-type allele was found in a TSC-associated renal carcinoma, which suggests that hamartin acts as a tumor suppressor.
  32. ncbi Mutational analysis of TSC1 and TSC2 genes in Japanese patients with tuberous sclerosis complex
    H Zhang
    Gene Research Center, Tottori University, Yonago, Japan
    J Hum Genet 44:391-6. 1999
    We have surveyed the mutations of TSC1 and TSC2 from 38 (25 sporadic, 11 familial, and 2 unknown) Japanese patients with tuberous sclerosis complex...
  33. pmc Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning
    Sheng Li Cai
    Department of Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, 78957, USA
    J Cell Biol 173:279-89. 2006
    ..Thus, tuberin bound by 14-3-3 in response to AKT phosphorylation is sequestered away from its membrane-bound activation partner (hamartin) and its target GTPase (Rheb) to relieve the growth inhibitory effects of this tumor suppressor.
  34. ncbi TSC2 missense mutations inhibit tuberin phosphorylation and prevent formation of the tuberin-hamartin complex
    M Nellist
    Department of Clinical Genetics, Erasmus University, 3015 GE Rotterdam, The Netherlands
    Hum Mol Genet 10:2889-98. 2001
    ..TSC1 and TSC2 encode two large novel proteins called hamartin and tuberin, respectively...
  35. ncbi Human bladder tumors with 2-hit mutations of tumor suppressor gene TSC1 and decreased expression of p27
    Hiroyuki Adachi
    Department of Urology, Shimane Medical University, Izumo, Japan
    J Urol 170:601-4. 2003
    ..chromosome 9 is known to be the most common finding in human bladder tumors, we studied the mutation of the tumor suppressor gene TSC1 (chromosome 9q34) in bladder tumors. Since another tumor suppressor gene, TSC2 (chromosome 16p13...
  36. ncbi Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2
    Attila Garami
    Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland
    Mol Cell 11:1457-66. 2003
    b>Tumor suppressor genes evolved as negative effectors of mitogen and nutrient signaling pathways, such that mutations in these genes can lead to pathological states of growth...
  37. ncbi Tuberous sclerosis complex (TSC) gene involvement in sporadic tumours
    M A Knowles
    Cancer Research UK Clinical Centre, St James s University Hospital, Beckett Street, Leeds LS9 7TF, UK
    Biochem Soc Trans 31:597-602. 2003
    In tuberous sclerosis patients, inactivation of the tuberous sclerosis complex tumour-suppressor genes TSC1 and TSC2 contributes to the development of a wide range of hamartomatous lesions...
  38. ncbi Pathological mutations in TSC1 and TSC2 disrupt the interaction between hamartin and tuberin
    A K Hodges
    Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK
    Hum Mol Genet 10:2899-905. 2001
    Critical functions of hamartin and tuberin, encoded by the TSC1 and TSC2 genes, are likely to be closely linked...
  39. ncbi Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products
    M van Slegtenhorst
    MGC Department of Clinical Genetics, Erasmus University, 3015GE Rotterdam, The Netherlands
    Hum Mol Genet 7:1053-7. 1998
    ..The TSC1 gene was recently identified and codes for hamartin, a novel protein with no significant homology to tuberin or any other known vertebrate protein...
  40. ncbi Analysis of all exons of TSC1 and TSC2 genes for germline mutations in Japanese patients with tuberous sclerosis: report of 10 mutations
    Y Yamashita
    Department of Experimental Pathology, Cancer Institute, Tokyo, Japan
    Am J Med Genet 90:123-6. 2000
    ..All mutations were expected to result in a truncated hamartin gene product...
  41. ncbi Comprehensive mutational analysis of the TSC1 gene: observations on frequency of mutation, associated features, and nonpenetrance
    J Kwiatkowska
    Division of Experimental Medicine and Medical Oncology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Ann Hum Genet 62:277-85. 1998
    We performed a comprehensive analysis for mutations in the TSC1 gene using Southern blot analysis, and SSCP and heteroduplex analysis of amplified exons in 13 families with genetic linkage to the TSC1 region, 22 small families without ..
  42. ncbi Hamartin, the tuberous sclerosis complex 1 gene product, interacts with polo-like kinase 1 in a phosphorylation-dependent manner
    Aristotelis Astrinidis
    Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    Hum Mol Genet 15:287-97. 2006
    Tuberous sclerosis complex (TSC) is a tumor suppressor gene syndrome caused by mutations in TSC1 and TSC2. Hamartin and tuberin, the products of TSC1 and TSC2, respectively, form heterodimers and inhibit the mammalian target of rapamycin...
  43. pmc Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs
    S L Dabora
    Genetics Laboratory, Division of Hematology, Brigham and Women s Hospital, Boston, MA, 02115, USA
    Am J Hum Genet 68:64-80. 2001
    Tuberous sclerosis (TSC) is a relatively common hamartoma syndrome caused by mutations in either of two genes, TSC1 and TSC2...
  44. ncbi Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin
    Han C Dan
    Department of Pathology, Molecular Oncology, and Drug Discovery Programs, University of South Florida College of Medicine, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA
    J Biol Chem 277:35364-70. 2002
    Normal cellular functions of hamartin and tuberin, encoded by the TSC1 and TSC2 tumor suppressor genes, are closely related to their direct interactions...
  45. pmc Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase
    Philippe P Roux
    Department of Cell Biology and Taplin Biological Mass Spectrometry Facility, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 101:13489-94. 2004
    Tuberous sclerosis complex (TSC) is a genetic disorder caused by mutations in either of the two tumor suppressor genes TSC1 or TSC2, which encode hamartin and tuberin, respectively...
  46. ncbi Characterization of the cytosolic tuberin-hamartin complex. Tuberin is a cytosolic chaperone for hamartin
    M Nellist
    Department of Clinical Genetics, Erasmus University, 3015 GE Rotterdam, The Netherlands
    J Biol Chem 274:35647-52. 1999
    ..Mutations to either the TSC1 or TSC2 gene are responsible for the disease. The TSC1 gene encodes hamartin, a 130-kDa protein without significant homology to other known mammalian proteins...
  47. ncbi Molecular genetics of renal carcinogenesis
    C Walker
    The University of Texas MD Anderson Cancer Center, Science Park Research Division, Smithville 78957, USA
    Toxicol Pathol 26:113-20. 1998
    ..Solid RCC of the clear cell type is associated with alterations in the VHL tumor suppressor gene and hereditary papillary RCC is associated with alterations of the c-met protooncogene...
  48. ncbi [The main etiopathogenic mechanisms of neurocutaneous diseases]
    F J Vicente
    , , Facultadde Medicina, Universidad de Navarra, Pamplona,
    Rev Neurol 25:S214-21. 1997
    ..Mutations in tumor suppressor genes play an important part in the development of hamartomatous and neoplastic lesions in neurofibromatosis ..
  49. ncbi Analysis of a polymorphism in the tuberous sclerosis (TSC2) gene does not predispose to schizophrenia
    R Przkora
    Department of Neuropathology, University of Bonn Medical Center, Germany
    Eur Arch Psychiatry Clin Neurosci 248:314-5. 1998
    The tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the development of malformations in various organs including the brain...
  50. ncbi Sensitivity of soft tissue sarcoma cell lines to chemotherapeutic agents: identification of ecteinascidin-743 as a potent cytotoxic agent
    W W Li
    Laboratories of Molecular Pharmacology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA
    Clin Cancer Res 7:2908-11. 2001
    ..Cell lines were also characterized as to expression of oncogenes and tumor suppressor genes to attempt to correlate sensitivity of these cell lines to ET-743 and other chemotherapeutic agents...
  51. ncbi Oncogenes and tumor suppressor genes
    G Klein
    Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden
    Acta Oncol 27:427-37. 1988
    ..DNA binding proteins, presumably involved in DNA replication may drive cell division after constitutive activation by retroviral insertion, chromosomal translocation or gene amplification (example: the myc-family)...
  52. ncbi Mutations in adrenocortical tumors
    M Reincke
    Medical Department II, University of Freiburg, Germany
    Horm Metab Res 30:447-55. 1998
    ..Oncogenes and tumor suppressor genes involved in adrenal carcinomas include mutations in the p53 tumor suppressor gene and rearrangements of ..
  53. ncbi Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: a clinicopathologic study of 26 cases and review of the literature
    Andrew L Folpe
    Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA
    Am J Surg Pathol 29:1558-75. 2005
    ..of tumors includes angiomyolipoma (AML), clear cell sugar tumor of the lung (CCST), lymphangioleiomyomatosis (LAM), and very rare tumors in other locations...
  54. ncbi Spontaneous mutation of cell oncogenes plays a minor role in neoplastic transformation of virus-induced murine T-cell lymphomas
    D Gasparotto
    Department of Experimental Oncology 1, Centro di Riferimento Oncologico, Aviano (PN, Italy
    Tumori 81:268-72. 1995
    ..However, molecular phenomena not strictly virus-determined, such as mutations in cellular oncogenes/tumor suppressor genes or chromosome aberrations, have been hypothesized to contribute to the achievement of the fully ..
  55. ncbi [Abnormalities of the p53, N-ras, DCC and FLT-3 genes in myelodysplastic syndromes]
    K Nakamura
    Department of 3rd Internal Medicine, Nippon Medical School, Tokyo, Japan
    J Nippon Med Sch 68:143-8. 2001
    ..is a multistep process that is characterized by both activation of oncogenes and inactivation of tumor suppressor genes...
  56. pmc Comparison of three rapamycin dosing schedules in A/J Tsc2+/- mice and improved survival with angiogenesis inhibitor or asparaginase treatment in mice with subcutaneous tuberous sclerosis related tumors
    Chelsey Woodrum
    Translational Medicine Division, Department of Medicine, Brigham and Women s Hospital, Karp Building, Boston, MA, USA
    J Transl Med 8:14. 2010
    Tuberous Sclerosis Complex (TSC) is an autosomal dominant tumor disorder characterized by the growth of hamartomas in various organs including the kidney, brain, skin, lungs, and heart...
  57. ncbi Rare loss of heterozygosity of the MTS1 and MTS2 tumor suppressor genes in differentiated human thyroid cancer
    K M Schulte
    Dept. of General and Trauma Surgery, Heinrich Heine University, , Germany
    Horm Metab Res 30:549-54. 1998
    Loss of heterozygosity (LOH) of the MTS1 (p16) tumor suppressor gene has been reported to occur frequently in thyroid cancer cell lines...
  58. ncbi Molecular genetics and human prostatic carcinoma
    V P Collins
    Ludwig Institute for Cancer Research, Karolinska Hospital, Stockholm, Sweden
    Acta Oncol 30:181-5. 1991
    ..Such genes have been named tumor suppressor genes...
  59. ncbi Genetic and clinical characteristics of multiple endocrine neoplasia type 1
    B Skogseid
    Department of Internal Medicine, University Hospital, Ludwig Institute for Cancer Research, Uppsala, Sweden
    Acta Oncol 30:485-8. 1991
    ..pancreatic endocrine and parathyroid tissue, which suggests that the MEN 1 gene belongs to the group of tumor suppressor genes (antioncogenes)...
  60. ncbi [Induction of gene expression of cancer-related genes by environmental stresses]
    H Matsumoto
    Department of Anatomy, Nara Medical University
    Biol Sci Space 8:94-102. 1994
    ....
  61. pmc Utility of [18F]2-fluoro-2-deoxyglucose-PET in sporadic and tuberous sclerosis-associated lymphangioleiomyomatosis
    Lisa R Young
    Department of Pulmonary, Critical Care, and Sleep Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
    Chest 136:926-33. 2009
    Mutations in tuberous sclerosis complex (TSC) genes are associated with dysregulated mammalian target of rapamycin (mTOR)/Akt signaling and unusual neoplasms called perivascular epithelioid cell tumors (PEComas), including ..
  62. doi Loss of heterozygosity on tuberous sclerosis complex genes in multifocal micronodular pneumocyte hyperplasia
    Takuo Hayashi
    Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
    Mod Pathol 23:1251-60. 2010
    ..pneumocyte hyperplasia is a rare pulmonary manifestation of tuberous sclerosis complex (TSC) that is a tumor suppressor gene disorder characterized by many hamartomas...
  63. ncbi Meta analysis of the relationship between tuberous sclerosis complex and renal cell carcinoma
    R Tello
    Department of Radiology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Eur J Radiol 27:131-8. 1998
    The association of angiomyolipoma with tuberous sclerosis complex (TSC) patients is well recognised...
  64. ncbi Loss of heterozygosity involves multiple tumor suppressor genes in human esophageal cancers
    Y Huang
    Department of Microbiology and Immunology, University of Maryland, Baltimore 21201
    Cancer Res 52:6525-30. 1992
    ..The targets of frequent or consistent subchromosomal deletions are believed to be tumor suppressor genes...
  65. pmc Biallelic TSC gene inactivation in tuberous sclerosis complex
    Peter B Crino
    Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Neurology 74:1716-23. 2010
    A pivotal developmental question is whether tubers in tuberous sclerosis complex (TSC) form by germline and somatic TSC1 or TSC2 gene mutations...
  66. ncbi Antitumor activity- and gene expression-based profiling of ecteinascidin Et 743 and phthalascidin Pt 650
    E J Martinez
    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
    Chem Biol 8:1151-60. 2001
    ..In HCT116 carrying the wild-type p53 tumor suppressor gene, the up-regulation of several p53-responsive genes was evident...
  67. ncbi Frequent loss of heterozygosity at the retinoblastoma locus in human esophageal cancers
    R F Boynton
    Department of Medicine, Gastroenterology Division, University of Maryland, Baltimore
    Cancer Res 51:5766-9. 1991
    Abnormalities in the retinoblastoma tumor suppressor gene (Rb) have been observed in a large number of human cancers. Loss of heterozygosity is a common mode of allelic inactivation of Rb and other tumor suppressor genes...
  68. pmc Mesenchymal-epithelial interactions involving epiregulin in tuberous sclerosis complex hamartomas
    Shaowei Li
    Department of Dermatology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 4712, USA
    Proc Natl Acad Sci U S A 105:3539-44. 2008
    ..with tuberous sclerosis complex (TSC) develop hamartomas containing biallelic inactivating mutations in either TSC1 or TSC2, resulting in mammalian target of rapamycin (mTOR) activation...
  69. pmc Insulin like growth factor-1-induced phosphorylation and altered distribution of tuberous sclerosis complex (TSC)1/TSC2 in C2C12 myotubes
    Mitsunori Miyazaki
    Center for Muscle Biology, Department of Physiology, University of Kentucky, Lexington, USA
    FEBS J 277:2180-91. 2010
    ..We found that IGF-1 treatment does not affect complex formation between TSC1 and TSC2, but rather IGF-1 induces an altered distribution of the TSC1/TSC2 complex in C2C12 myotubes...
  70. pmc The tuberous sclerosis proteins regulate formation of the primary cilium via a rapamycin-insensitive and polycystin 1-independent pathway
    Tiffiney R Hartman
    Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19090, USA
    Hum Mol Genet 18:151-63. 2009
    Tuberous sclerosis complex (TSC) is a tumor suppressor gene syndrome in which severe renal cystic disease can occur...
  71. ncbi Infantile spasm-associated microencephaly in tuberous sclerosis complex and cortical dysplasia
    P S Chandra
    Division of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
    Neurology 68:438-45. 2007
    In children with and without infantile spasms, this study determined brain volumes and cell densities in epilepsy surgery patients with tuberous sclerosis complex (TSC) and cortical dysplasia with balloon cells (CD).
  72. ncbi Mutational and radiographic analysis of pulmonary disease consistent with lymphangioleiomyomatosis and micronodular pneumocyte hyperplasia in women with tuberous sclerosis
    D N Franz
    Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    Am J Respir Crit Care Med 164:661-8. 2001
    ..TSC2 mutations were identified in all cyst-positive patients who were tested (n = 8), whereas both TSC1 and TSC2 mutations were found in patients with nodular disease...
  73. doi Lymphangioleiomyomatosis and tuberous sclerosis complex
    Dimitrios Chorianopoulos
    1st Department of Respiratory Medicine, University of Athens Medical School, Sotiria General Hospital, Athens, Greece
    Lung 186:197-207. 2008
    ..TSC is caused by mutations in two genes, TSC1 on chromosome 9q34 and TSC2 on 16p13. Both of these genes are tumor suppressor genes encoding hamartin (TSC1) and tuberin (TSC2)...
  74. pmc CT of sclerotic bone lesions: imaging features differentiating tuberous sclerosis complex with lymphangioleiomyomatosis from sporadic lymphangioleiomymatosis
    Nilo A Avila
    Radiology Service, Washington D C Veterans Affairs Medical Center, 50 Irving St NW, Room BH 223, Washington, DC 20422, USA
    Radiology 254:851-7. 2010
    ..evident at body computed tomography (CT) are of value as a diagnostic criterion of tuberous sclerosis complex (TSC) and in the differentiation of TSC with lymphangioleiomyomatosis (LAM) from sporadic LAM...
  75. ncbi Interferon beta augments tuberous sclerosis complex 2 (TSC2)-dependent inhibition of TSC2-null ELT3 and human lymphangioleiomyomatosis-derived cell proliferation
    Elena A Goncharova
    Department of Medicine, University of Pennsylvania, TRL Suite 1200, 125 South 31st Street, Philadelphia, PA 19104, USA
    Mol Pharmacol 73:778-88. 2008
    ..Mutational inactivation of tumor suppressor tuberous sclerosis complex 2 (TSC2) in LAM constitutively activates the mammalian target of rapamycin (mTOR)/..
  76. doi Prevalence of subependymal giant cell tumors in patients with tuberous sclerosis and a review of the literature
    M E A P M Adriaensen
    Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands
    Eur J Neurol 16:691-6. 2009
    To investigate the prevalence of subependymal giant cell ependymomas (SEGA) in patients with tuberous sclerosis complex (TSC).
  77. pmc Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis
    T Carsillo
    Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia PA 19111, USA
    Proc Natl Acad Sci U S A 97:6085-90. 2000
    ..TSC2 loss of heterozygosity in 7 of 13 (54%) of angiomyolipomas from sporadic LAM patients, suggesting that LAM and TSC could have a common genetic basis...
  78. doi The tuberous sclerosis gene products hamartin and tuberin are multifunctional proteins with a wide spectrum of interacting partners
    Margit Rosner
    Medical Genetics, Obstetrics and Gynecology, Medical University of Vienna, Wahringer Gurtel 18 20, Vienna, Austria
    Mutat Res 658:234-46. 2008
    Mutations in the tumor suppressor genes TSC1 and TSC2, encoding hamartin and tuberin, respectively, cause the tumor syndrome tuberous sclerosis with similar phenotypes...
  79. ncbi The tuberous sclerosis complex (TSC) pathway and mechanism of size control
    C J Potter
    Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA
    Biochem Soc Trans 31:584-6. 2003
    ..PTEN (phosphatase and tensin homologue deleted on chromosome 10), and the tuberous sclerosis complex (TSC) genes, Tsc1 and Tsc2...
  80. pmc Tuberous sclerosis preclinical studies: timing of treatment, combination of a rapamycin analog (CCI-779) and interferon-gamma, and comparison of rapamycin to CCI-779
    Michael P Messina
    Translational Medicine Division, Department of Medicine, Brigham and Women s Hospital, Karp Family Research Laboratories, Boston, MA, USA
    BMC Pharmacol 7:14. 2007
    ..TSC is caused by a mutation in either the TSC1 or TSC2 genes, whose products, hamartin and tuberin, function as negative regulators in the highly-conserved mammalian target of rapamycin (mTOR) ..
  81. pmc Signaling events downstream of mammalian target of rapamycin complex 2 are attenuated in cells and tumors deficient for the tuberous sclerosis complex tumor suppressors
    Jingxiang Huang
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Massachusetts General Hospital, Boston, Massachusetts 02115, USA
    Cancer Res 69:6107-14. 2009
    Mutations in the TSC1 and TSC2 tumor suppressor genes give rise to the neoplastic disorders tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis...
  82. pmc Recognition of tuberous sclerosis in adult women: delayed presentation with life-threatening consequences
    Diane Seibert
    Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
    Ann Intern Med 154:806-13, W-294. 2011
    Tuberous sclerosis complex (TSC) is associated with tumor development in the brain, retina, kidney, skin, heart, and lung...
  83. ncbi Clinical symptoms of tuberous sclerosis complex in patients with an identical TSC2 mutation
    Paulina Rok
    Department of Child Neurology and Epileptology, The Children s Memorial Health Institute, Warsaw, Poland
    Med Sci Monit 11:CR230-234. 2005
    ..TSC is caused by mutations in either of two tumor suppressor genes: TSC1 or TSC2...
  84. doi Therapeutic targeting of mTOR in tuberous sclerosis
    Julian R Sampson
    Institute of Medical Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
    Biochem Soc Trans 37:259-64. 2009
    ..Both diseases are caused by mutations of TSC1 or TSC2 (TSC is tuberous sclerosis complex) that impair GAP (GTPase-activating protein) activity of the TSC1-TSC2 ..
  85. pmc MCP-1 overexpressed in tuberous sclerosis lesions acts as a paracrine factor for tumor development
    Shaowei Li
    Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
    J Exp Med 202:617-24. 2005
    Patients with tuberous sclerosis complex (TSC) develop hamartomatous tumors showing loss of function of the tumor suppressor TSC1 (hamartin) or TSC2 (tuberin) and increased angiogenesis, fibrosis, and abundant mononuclear phagocytes...
  86. doi Cyst-like tubers are associated with TSC2 and epilepsy in tuberous sclerosis complex
    Catherine J Chu-Shore
    Carol and James Herscot Center for Tuberous Sclerosis Complex, 175 Cambridge Street, Suite 340, Boston, MA 02114, USA
    Neurology 72:1165-9. 2009
    Tuberous sclerosis complex (TSC) is a genetic condition characterized by the presence of hamartomatous lesions in multiple organs, including tubers in the brain. The majority of patients with TSC have epilepsy...
  87. ncbi Cells derived from tuberous sclerosis show a prolonged S phase of the cell cycle and increased apoptosis
    M Wataya-Kaneda
    Department of Dermatology, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan
    Arch Dermatol Res 293:460-9. 2001
    ..Although the disease-determining genes TSC1 and TSC2 have been isolated, the molecular pathogenesis of the disease is not understood...
  88. ncbi [The results of recent research in neurocutaneous syndromes]
    K Ohno
    Department of Neurobiology, School of Life Sciences, Tottori University Faculty of Medicine, Yonago
    No To Hattatsu 30:109-14. 1998
    ..Evidence suggests that these genes are tumor suppressor genes...
  89. ncbi Prognostic factors in squamous cell carcinomas of the head and neck
    M Liu
    Department of ENT, Institute Therasse University Clinics of Mont-Godinne, Yvoir, Belgium
    Acta Otorhinolaryngol Belg 53:155-60. 1999
    ....
  90. pmc Tsc2 gene inactivation causes a more severe epilepsy phenotype than Tsc1 inactivation in a mouse model of tuberous sclerosis complex
    Ling Hui Zeng
    Department of Pharmacy, Zhejiang University City College, Hangzhou, Zhejiang 310015, China
    Hum Mol Genet 20:445-54. 2011
    ..Two genes, TSC1 and TSC2, encoding the proteins hamartin and tuberin, respectively, have been identified as causing TSC...
  91. ncbi Analysis of 65 tuberous sclerosis complex (TSC) patients by TSC2 DGGE, TSC1/TSC2 MLPA, and TSC1 long-range PCR sequencing, and report of 28 novel mutations
    Nanna D Rendtorff
    Department of Medical Genetics, John F Kennedy Institute, Glostrup, Denmark
    Hum Mutat 26:374-83. 2005
    ..An inactivating mutation in either of two tumor-suppressor genes-TSC1 and TSC2-is the cause of this syndrome, with TSC2 mutations accounting for 80-90% of all mutations...
  92. ncbi A mouse model of tuberous sclerosis 1 showing background specific early post-natal mortality and metastatic renal cell carcinoma
    Catherine Wilson
    Department of Medical Genetics, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
    Hum Mol Genet 14:1839-50. 2005
    ..We detected loss of the wild-type Tsc1 allele and elevated levels of p-mTOR and p-S6 in lesions from Tsc1+/- mice. This new murine model of hamartin deficiency exhibits a more severe phenotype than existing models.
  93. doi Are neuroendocrine tumours a feature of tuberous sclerosis? A systematic review
    Dorota Dworakowska
    Barts and the London School of Medicine, Centre for Endocrinology, London EC1M 6BQ, UK
    Endocr Relat Cancer 16:45-58. 2009
    ..3, which encode for hamartin and tuberin respectively...
  94. pmc Tuberous sclerosis complex tumor suppressor-mediated S6 kinase inhibition by phosphatidylinositide-3-OH kinase is mTOR independent
    Anja Jaeschke
    Cancer Research UK Centre for Cell and Molecular Biology, Institute for Cancer Research, 237 Fulham Road, London SW3 6JB, UK
    J Cell Biol 159:217-24. 2002
    ..Principally, such negative control mechanisms are represented by tumor suppressor genes, which normally act to constrain cell proliferation (Macleod, K. 2000. Curr. Opin. Genet. Dev...
  95. pmc Tuberous sclerosis complex activity is required to control neuronal stress responses in an mTOR-dependent manner
    Alessia Di Nardo
    The F M Kirby Neurobiology Center, Department of Neurology, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Neurosci 29:5926-37. 2009
    Tuberous sclerosis complex (TSC) is a neurogenetic disorder caused by loss-of-function mutations in either the TSC1 or TSC2 genes and frequently results in prominent CNS manifestations, including epilepsy, mental retardation, and autism ..
  96. doi Rapamycin as a therapy of choice after renal transplantation in a patient with tuberous sclerosis complex
    A Tarasewicz
    Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, Poland
    Transplant Proc 41:3677-82. 2009
    ..TSC is a genetic disorder, caused by mutations of TSC1 or TSC2 genes. Products of these genes, hamartin and tuberin, create a complex that inhibits mammalian target of rapamycin (mTOR), a key protein engaged in ..
  97. ncbi Tuberous sclerosis-2 tumor suppressor modulates ERK and B-Raf activity in transformed renal epithelial cells
    Hae Seong Yoon
    Center for Molecular and Cellular Toxicology, Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Texas 78712, USA
    Am J Physiol Renal Physiol 286:F417-24. 2004
    The tuberous sclerosis-2 (Tsc-2) gene is a suppressor of renal tumorigenesis and an early target of reactive oxygen species-induced renal cancer...
  98. pmc Zebrafish model of tuberous sclerosis complex reveals cell-autonomous and non-cell-autonomous functions of mutant tuberin
    Seok Hyung Kim
    Vanderbilt University, Department of Biological Sciences, Nashville, TN 37232, USA
    Dis Model Mech 4:255-67. 2011
    Tuberous sclerosis complex (TSC) is an autosomal dominant disease caused by mutations in either the TSC1 (encodes hamartin) or TSC2 (encodes tuberin) genes...
  99. ncbi Tuberous sclerosis complex: a review of the management of epilepsy with emphasis on surgical aspects
    Mary B Connolly
    Division of Pediatric Neurology, Department of Pediatrics, University of British Columbia and British Columbia s Children s Hospital, Vancouver, British Columbia, Canada
    Childs Nerv Syst 22:896-908. 2006
    To review the management of epilepsy in patients with tuberous sclerosis complex (TSC) with an emphasis on surgical aspects, neuropathology, and pathogenesis.
  100. ncbi Expression profiling in tuberous sclerosis complex (TSC) knockout mouse astrocytes to characterize human TSC brain pathology
    Kevin C Ess
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Glia 46:28-40. 2004
    ..specific markers of aberrant neuroglial cell differentiation in TSC, we employed gene expression profiling on Tsc1 conditional knockout (Tsc1(GFAP)CKO) mouse astrocytes...
  101. ncbi Localization of tuberous sclerosis 2 mRNA and its protein product tuberin in normal human brain and in cerebral lesions of patients with tuberous sclerosis
    C Kerfoot
    Department of Pathology and Laboratory Medicine Neuropathology, UCLA Medical Center 90095, USA
    Brain Pathol 6:367-75. 1996
    ..3. TSC2 has been cloned, sequenced and encodes a protein (tuberin) which functions as a tumor suppressor. We have analyzed the distribution of TSC2 mRNA and tuberin in the brains of TSC patients and non-affected ..

Research Grants84

  1. Mechanisms of Brain Dysfunction in Tuberous Sclerosis
    Michael Wong; Fiscal Year: 2007
    ..To understand the contribution of glial cells to TSC brain dysfunction, we developed a novel mouse model of TSC (Tsc1[GFAP]CKO mice), in which Tsd inactivation in glia results in abnormalities in glial growth, proliferation, and ..
  2. mTOR-containing Protein Complexes in the Pathogenesis of Tuberous Sclerosis
    ARNOLD KRISTOF; Fiscal Year: 2007
    ..Loss or inactivation of the TSC1 or TSC2 tumor suppressor genes leads to abnormally high activity of the protein mammalian target of rapamycin (mTOR), and excessive ..
  3. Regulation of the mTOR Pathway By Nutrients
    David Sabatini; Fiscal Year: 2009
    ..Many cancer-promoting lesions activate the mTORC1 pathway. Most notably, the TSC1-TSC2 tumor suppressor complex--whose inactivation causes Tuberous Sclerosis Complex (TSC) and the related disease ..
  4. Regulation of the mTOR Pathway By Nutrients
    David M Sabatini; Fiscal Year: 2010
    ..Many cancer-promoting lesions activate the mTORC1 pathway. Most notably, the TSC1-TSC2 tumor suppressor complex--whose inactivation causes Tuberous Sclerosis Complex (TSC) and the related disease ..
  5. Identifying Epileptogenic Tubers in TSC
    Harry T Chugani; Fiscal Year: 2010
    ..TSC is an autosomal dominant inherited disorder resulting from mutations in at least two different genes, TSC1 and TSC2...
  6. PHASE III TRIAL FO SIROLIMUS IN LYMPHANGIOLEIOMYLMATOSIS
    Francis McCormack; Fiscal Year: 2007
    ..Functional deficiencies of the encoded products, tuberin or hamartin, result in dysregulated signaling through the Akt pathway which controls cell growth, movement and survival...
  7. PHASE III TRIAL FO SIROLIMUS IN LYMPHANGIOLEIOMYLMATOSIS
    Francis McCormack; Fiscal Year: 2009
    ..Functional deficiencies of the encoded products, tuberin or hamartin, result in dysregulated signaling through the Akt pathway which controls cell growth, movement and survival...
  8. Tuberin and hamartin in rapamycin-sensitive & rapamycin-insensitive smooth muscle
    Geraldine Finlay; Fiscal Year: 2009
    ..Hamartin and tuberin are highly expressed in smooth muscle and are encoded by the tumor suppressor genes, Tuberous Sclerosis Complex-1 and -2 respectively (TSC1; TSC2)...
  9. Tuberin and hamartin in rapamycin-sensitive & rapamycin-insensitive smooth muscle
    Geraldine A Finlay; Fiscal Year: 2010
    ..Hamartin and tuberin are highly expressed in smooth muscle and are encoded by the tumor suppressor genes, Tuberous Sclerosis Complex-1 and -2 respectively (TSC1;TSC2)...
  10. The Role of TSC2 and Rho GTPases in LAM
    VERA KRYMSKAYA; Fiscal Year: 2009
    ..studies in elucidating the molecular mechanism of LAM led to the identification of essential function of the tumor suppressor tuberous sclerosis complex 2 (TSC2) as a negative regulator of mammalian target of rapamycin (mTOR)/p70 S6 ..
  11. The Role of TSC2 and Rho GTPases in LAM
    Vera P Krymskaya; Fiscal Year: 2010
    ..studies in elucidating the molecular mechanism of LAM led to the identification of essential function of the tumor suppressor tuberous sclerosis complex 2 (TSC2) as a negative regulator of mammalian target of rapamycin (mTOR)/p70 S6 ..
  12. Utility of Rapamycin for the Treatment of Renal Angiomy*
    John Bissler; Fiscal Year: 2004
    ..by well-characterized inactivating mutations at genetic loci that encode the interacting proteins, tuberin or hamartin. Elegant studies have recently elucidated the pivotal role of the tuberin/hamartin complex in the checkpoint ..
  13. Tuberous Sclerosis: Mutations and Murine Models
    David Kwiatkowski; Fiscal Year: 2007
    Tuberous sclerosis (TSC) is an autosomal dominant tumor suppressor gene syndrome affecting 1 in 6,000 births, characterized by development of distinctive benign tumors (hamartomas) and malformations (hamartias) in multiple organ systems...
  14. Role of p70 S6 Kinase in Regulating LAM Cell Growth
    Vera P Krymskaya; Fiscal Year: 2010
    ..LAM is associated with mutational inactivation of the tumor suppressors tuberous sclerosis complex 1 (TSC1) and TSC2;loss of TSC2, in particular, is correlated with disease severity and tumor growth...
  15. Role of p70 S6 Kinase in Regulating LAM Cell Growth
    VERA KRYMSKAYA; Fiscal Year: 2009
    ..LAM is associated with mutational inactivation of the tumor suppressors tuberous sclerosis complex 1 (TSC1) and TSC2; loss of TSC2, in particular, is correlated with disease severity and tumor growth...
  16. Role of p70 S6 Kinase in Regulating LAM Cell Growth
    VERA KRYMSKAYA; Fiscal Year: 2007
    ..LAM is associated with mutational inactivation of the tumor suppressors tuberous sclerosis complex 1 (TSC1) and TSC2; loss of TSC2, in particular, is correlated with disease severity and tumor growth...
  17. CNS Manifestations of Tuberous Sclerosis Complex
    VICKY WHITTEMORE; Fiscal Year: 2005
    ..The basic biology of LAM indicates that the TSC2, and perhaps the TSC1 gene, play a significant role in LAM, so the last two LAMposiums have included numerous sessions focused on the ..
  18. Tuberous Sclerosis Complex Conference: From Genes to New Therapeutics
    VICKY WHITTEMORE; Fiscal Year: 2007
    ..diseases to determine what can be learned from work in other research areas Discuss the research on the role of the TSC1/2 genes and their protein products in the mTOR signaling pathway Review our current knowledge of variation of the ..
  19. Cell Growth Signaling in Cancer Development
    David M Sabatini; Fiscal Year: 2010
    ..Most notably, the TSC1-TSC2 tumor suppressor complex--whose inactivation causes the tumor- prone syndrome Tuberous Sclerosis Complex (TSC) and the related ..
  20. mTOR-containing Protein Complexes in the Pathogenesis of Tuberous Sclerosis
    ARNOLD KRISTOF; Fiscal Year: 2010
    ..Loss or inactivation of the TSC1 or TSC2 tumor suppressor genes leads to abnormally high activity of the protein mammalian target of rapamycin (mTOR), and excessive ..
  21. MOLECULAR BASIS OF LYMPHANGIOMYOMATOSIS
    ELIZABETH HENSKE; Fiscal Year: 2002
    ..TSC1 and TSC2 appear to be tumor suppressor genes...
  22. MOLECULAR BASIS OF LYMPHANGIOMYOMATOSIS
    ELIZABETH HENSKE; Fiscal Year: 2003
    ..Recent work by another group has demonstrated that hamartin (the TSC1 gene product) interacts with the moesin-ezrin-radixin family of cytoskeletal proteins, activates the ..
  23. MOLECULAR BASIS OF LYMPHANGIOMYOMATOSIS
    ELIZABETH HENSKE; Fiscal Year: 2006
    ..Recent work by another group has demonstrated that hamartin (the TSC1 gene product) interacts with the moesin-ezrin-radixin family of cytoskeletal proteins, activates the ..
  24. Dissecting the Molecular Pathology of LAM Disease
    Daniel Noonan; Fiscal Year: 2005
    ..4) Characterization of TSC1?s role in the TSC2/calmodulin signaling pathway...
  25. Multicenter clinical trials for TSC & related disorders
    Sandra Dabora; Fiscal Year: 2007
    ..to implement the first multicenter clinical trial for the multisystem familial tumor disorder, tuberous sclerosis (TSC)...
  26. The 2007 LAM Foundation Lymphangioleiomyomatosis International Research Conferenc
    Francis McCormack; Fiscal Year: 2007
    The LAM Foundation 2007 Lymphangioleiomyomatosis International Research Conference will focus on the molecular mechanisms of genetic mutation, metastasis and cystic lung destruction that occur in the fatal lung disease of women, ..
  27. Lymphangioleiomyomatosis Research Conference 2006
    Francis McCormack; Fiscal Year: 2006
    The LAM Foundation 2006 Lymphangioleiomyomatosis International Research Conference will focus on the molecular mechanisms of smooth muscle proliferation and cystic lung destruction that occur in the fatal lung disease of women, ..
  28. Molecular Pathogenesis of the Hamartoma Syndromes
    David Kwiatkowski; Fiscal Year: 2007
    ..that contribute to tumor development and physiology in the hamartoma syndromes resulting from loss of the tumor suppressor genes TSC1, TSC2, LKB1, and PTEN, and to identify and explore potential therapeutic targets...
  29. Molecular Genetics of Inherited Neurological Diseases
    Xandra Breakefield; Fiscal Year: 2005
    ..mouse models of these diseases will be used to understand physiologic changes associated with loss of these tumor suppressor genes and to provide a platform for therapeutic strategies...
  30. Mechanisms of Brain Dysfunction in Tuberous Sclerosis
    Michael Wong; Fiscal Year: 2010
    Tuberous Sclerosis Complex (TSC) is one of the most common genetic causes of epilepsy. In addition, epilepsy in TSC is typically very severe and intractable to available therapies...
  31. Roles of Tuberin (TSC2), Hamartin (TSC1), and Rheb in Renal Cyst Pathogenesis
    Elizabeth P Henske; Fiscal Year: 2010
    ..sclerosis complex (TSC) is caused by germline inactivating mutations in the TSC1 or TSC2 genes, which encode hamartin (TSC1) and tuberin (TSC2), respectively...
  32. Novel in vitro and xenograft models to study treatments for tuberous sclerosis
    Thomas Darling; Fiscal Year: 2007
    Tuberous sclerosis complex (TSC) is a tumor syndrome that affects about 1 in 6000 live births...
  33. IMAGING TRYPTOPHAN METABOLISM IN TUBEROUS SCLEROSIS
    Diane Chugani; Fiscal Year: 2003
    ..is an autosomal dominant inherited disorder, now known to result from mutations in at least two different genes, TSC1 and TSC2...
  34. Molecular Etiology of Leiomyoma Uteri
    Cheryl Walker; Fiscal Year: 2007
    ..Loss of the tuberous sclerosis complex 2 (TSC-2) tumor suppressor gene results in the development of leiomyoma uteri in the Eker rat model for this disease...
  35. GENES CONTROLLING NEOPLASIA OF THE INTESTINAL EPITHELIUM
    William Dove; Fiscal Year: 2007
    ..Our studies in the Min mouse strain have highlighted two new pathways by which the activity of the tumor suppressor gene Apc is lost: homologous somatic recombination and apparent epigenetic silencing...
  36. Prevention of prostate cancer growth by a plant alkaloid
    Partha P Banerjee; Fiscal Year: 2010
    ..However, it is becoming clear that epigenetic inactivation of various tumor suppressor genes could play pivotal role in the development of various cancers including prostate cancer...
  37. Structural consequences of TSC gene mutations in brain
    Peter B Crino; Fiscal Year: 2010
    Tuberous sclerosis complex (TSC) is an autosomal disorder resulting from mutations in the TSC1 or TSC2 genes that is associated with epilepsy, cognitive disability, and autism...
  38. Mouse Models of the Neuropathology of Tuberous Sclerosis Complex
    Michael Gambello; Fiscal Year: 2009
    ..Patients have mutations in either the TSC1 or TSC2 gene, encoding the proteins hamartin and tuberin, and have similar, but not identical, phenotypes...