Cdkn2a

Summary

Gene Symbol: Cdkn2a
Description: cyclin-dependent kinase inhibitor 2A
Alias: ARF-INK4a, Arf, INK4a-ARF, Ink4a/Arf, MTS1, Pctr1, p16, p16(INK4a), p16INK4a, p19, p19ARF, CDK4I, cyclin-dependent kinase 4 inhibitor A, cyclin-dependent kinase inhibitor 2A (p16, inhibits CDK4), cyclin-dependent kinase inhibitor 2A, isoforms 1/2, cyclin-dependent kinase inhibitor protein, mitochondrial smARF, p16-INK4, p16-INK4a
Species: mouse

Top Publications

  1. ncbi Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma
    Andrew J Aguirre
    Department of Medical Oncology, Dana Farber Cancer Institute and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Genes Dev 17:3112-26. 2003
  2. ncbi Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice
    Sunil R Hingorani
    Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cancer Cell 7:469-83. 2005
  3. ncbi Loss of p16Ink4a with retention of p19Arf predisposes mice to tumorigenesis
    N E Sharpless
    Departments of Adult Oncology, Medicine and Genetics, Harvard Medical School and the Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 413:86-91. 2001
  4. ncbi Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
    M Serrano
    Cold Spring Harbor Laboratory, New York 11724, USA
    Cell 88:593-602. 1997
  5. ncbi Tumor-initiated inflammation overrides protective adaptive immunity in an induced melanoma model in mice
    Saïdi M Soudja
    Centre d immunologie de Marseille Luminy, Universite de la Mediterranee, Institut National de la Sante et de la Recherche Medicale, U631 Centre National de la Recherche Scientifique, UMR6102, Marseille, France
    Cancer Res 70:3515-25. 2010
  6. ncbi Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a
    Viktor Janzen
    Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114, USA
    Nature 443:421-6. 2006
  7. ncbi ARF functions as a melanoma tumor suppressor by inducing p53-independent senescence
    Linan Ha
    Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, MD 20892 4264, USA
    Proc Natl Acad Sci U S A 104:10968-73. 2007
  8. ncbi Loss of Arf causes tumor progression of PDGFB-induced oligodendroglioma
    E Tchougounova
    Rudbeck Laboratory, Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden
    Oncogene 26:6289-96. 2007
  9. ncbi Pancreatic cancer and precursor pancreatic intraepithelial neoplasia lesions are devoid of primary cilia
    E Scott Seeley
    Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03756, USA
    Cancer Res 69:422-30. 2009
  10. ncbi Cooperative effects of INK4a and ras in melanoma susceptibility in vivo
    L Chin
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Genes Dev 11:2822-34. 1997

Research Grants

  1. Molecular dissection of pancreatic ductal adenocarcinoma
    Brian Lewis; Fiscal Year: 2009
  2. Mouse Model of Pancreatic Cancer Progression-Maintenance
    Nabeel Bardeesy; Fiscal Year: 2007
  3. Melanoma in p16INK4a and p19ARF Deficient Mice
    NORMAN SHARPLESS; Fiscal Year: 2006
  4. Molecular mediators of metastasis in hepatocellular carcinoma
    Brian Lewis; Fiscal Year: 2009
  5. The role of p16INK4a in mammalian aging
    NORMAN SHARPLESS; Fiscal Year: 2007
  6. Molecular mediators of metastasis in hepatocellular carcinoma
    Brian Lewis; Fiscal Year: 2007
  7. A flexible somatic and sporadic mouse model for pancreatic ductal adenocarcinoma
    Brian Lewis; Fiscal Year: 2007
  8. The role of p16INK4a in mammalian aging
    Norman Edward Sharpless; Fiscal Year: 2010
  9. Molecular dissection of pancreatic ductal adenocarcinoma
    Brian Lewis; Fiscal Year: 2009
  10. Molecular dissection of pancreatic ductal adenocarcinoma
    Brian C Lewis; Fiscal Year: 2010

Scientific Experts

Detail Information

Publications126 found, 100 shown here

  1. ncbi Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma
    Andrew J Aguirre
    Department of Medical Oncology, Dana Farber Cancer Institute and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Genes Dev 17:3112-26. 2003
    ..pancreas-specific Cre-mediated activation of a mutant Kras allele (KrasG12D) and deletion of a conditional Ink4a/Arf tumor suppressor allele...
  2. ncbi Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice
    Sunil R Hingorani
    Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cancer Cell 7:469-83. 2005
    ..These findings have clear implications for understanding mechanisms of disease pathogenesis, and for the development of detection and targeted treatment strategies...
  3. ncbi Loss of p16Ink4a with retention of p19Arf predisposes mice to tumorigenesis
    N E Sharpless
    Departments of Adult Oncology, Medicine and Genetics, Harvard Medical School and the Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 413:86-91. 2001
    The cyclin-dependent kinase inhibitor p16INK4a can induce senescence of human cells, and its loss by deletion, mutation or epigenetic silencing is among the most frequently observed molecular lesions in human cancer...
  4. ncbi Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
    M Serrano
    Cold Spring Harbor Laboratory, New York 11724, USA
    Cell 88:593-602. 1997
    ..primary cells by ras requires either a cooperating oncogene or the inactivation of tumor suppressors such as p53 or p16. Here we show that expression of oncogenic ras in primary human or rodent cells results in a permanent G1 arrest...
  5. ncbi Tumor-initiated inflammation overrides protective adaptive immunity in an induced melanoma model in mice
    Saïdi M Soudja
    Centre d immunologie de Marseille Luminy, Universite de la Mediterranee, Institut National de la Sante et de la Recherche Medicale, U631 Centre National de la Recherche Scientifique, UMR6102, Marseille, France
    Cancer Res 70:3515-25. 2010
    ..immune system on two differentially aggressive melanomas developing in mice on conditional deletion of the INK4A/ARF tumor suppressor gene, with concomitant expression of oncogene H-Ras(G12V) and a natural cancer-germline tumor ..
  6. ncbi Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a
    Viktor Janzen
    Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114, USA
    Nature 443:421-6. 2006
    ..Here we report that the cyclin-dependent kinase inhibitor p16INK4a, the level of which was previously noted to increase in other cell types with age, accumulates and modulates ..
  7. ncbi ARF functions as a melanoma tumor suppressor by inducing p53-independent senescence
    Linan Ha
    Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, MD 20892 4264, USA
    Proc Natl Acad Sci U S A 104:10968-73. 2007
    ..in its advanced disseminated form, mutation/deletion of p53 is relatively rare, whereas its positive regulator ARF is often lost...
  8. ncbi Loss of Arf causes tumor progression of PDGFB-induced oligodendroglioma
    E Tchougounova
    Rudbeck Laboratory, Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden
    Oncogene 26:6289-96. 2007
    ..In high-grade gliomas, the subsequent loss of the INK4a-ARF locus is one of the most common mutations...
  9. ncbi Pancreatic cancer and precursor pancreatic intraepithelial neoplasia lesions are devoid of primary cilia
    E Scott Seeley
    Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03756, USA
    Cancer Res 69:422-30. 2009
    ..Thus, arrested ciliogenesis is a cardinal feature of PDAC and its precursor PanIN lesions, does not require ongoing proliferation, and could potentially be targeted pharmacologically...
  10. ncbi Cooperative effects of INK4a and ras in melanoma susceptibility in vivo
    L Chin
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Genes Dev 11:2822-34. 1997
    The familial melanoma gene (INK4a/MTS1/CDKN2) encodes potent tumor suppressor activity. Although mice null for the ink4a homolog develop a cancer-prone condition, a pathogenetic link to melanoma susceptibility has yet to be established...
  11. ncbi ARF stimulates XPC to trigger nucleotide excision repair by regulating the repressor complex of E2F4
    Carmen Dominguez-Brauer
    Department of Biochemistry and Molecular Genetics, University of Illinois, College of Medicine, M C 669, 900 S Ashland Avenue, Chicago, Illinois 60607, USA
    EMBO Rep 10:1036-42. 2009
    The tumour suppressor ARF (alternative reading frame), which is mutated or silenced in various tumours, has a crucial role in tumour surveillance to suppress unwarranted cell growth and proliferation...
  12. ncbi An inducible mouse model of melanoma expressing a defined tumor antigen
    Ivo J Huijbers
    Ludwig Institute for Cancer Research and Cellular Genetics Unit, Universite Catholique de Louvain, Brussels, Belgium
    Cancer Res 66:3278-86. 2006
    ..melanocytes, we aimed at simultaneously activating the Ras pathway and inactivating tumor suppressor Ink4a/Arf, thereby reproducing two genetic events frequently observed in human melanoma. The melanomas are induced by s.c...
  13. ncbi Activated TNF-alpha/NF-kappaB signaling via down-regulation of Fas-associated factor 1 in asbestos-induced mesotheliomas from Arf knockout mice
    Deborah A Altomare
    Human Genetics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    Proc Natl Acad Sci U S A 106:3420-5. 2009
    The human CDKN2A locus encodes 2 distinct proteins, p16(INK4A) and p14(ARF) [mouse p19(Arf)], designated INK4A (inhibitor of cyclin dependent kinase 4) and ARF (alternative reading frame) here, that are translated from alternatively ..
  14. ncbi INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53
    C A Schmitt
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Genes Dev 13:2670-7. 1999
    The INK4a/ARF locus encodes upstream regulators of the retinoblastoma and p53 tumor suppressor gene products...
  15. ncbi Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2
    T Kamijo
    Howard Hughes Medical Institute, St Jude Children s Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA
    Proc Natl Acad Sci U S A 95:8292-7. 1998
    The INK4a-ARF locus encodes two proteins, p16(INK4a) and p19(ARF), that restrain cell growth by affecting the functions of the retinoblastoma protein and p53, respectively...
  16. ncbi Cell type-specific tumor suppression by Ink4a and Arf in Kras-induced mouse gliomagenesis
    Lene Uhrbom
    Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala, Sweden
    Cancer Res 65:2065-9. 2005
    Homozygous deletion of the INK4a-ARF locus is one of the most frequent mutations found in human glioblastoma...
  17. ncbi Bmi-1 over-expression in neural stem/progenitor cells increases proliferation and neurogenesis in culture but has little effect on these functions in vivo
    Shenghui He
    Howard Hughes Medical Institute, Department of Internal Medicine, Center for Stem Cell Biology, University of Michigan, 5435 Life Sciences Institute, 210 Washtenaw Ave, Ann Arbor, MI 48109 2216, USA
    Dev Biol 328:257-72. 2009
    ..pronounced effects of Bmi-1 over-expression in culture were largely attributable to the attenuated induction of p16(Ink4a) and p19(Arf) in culture, proteins that are generally not expressed by neural stem/progenitor cells in young ..
  18. ncbi Rescue of key features of the p63-null epithelial phenotype by inactivation of Ink4a and Arf
    Xiaohua Su
    Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    EMBO J 28:1904-15. 2009
    ..Here, we show that inactivation of p63 in mice is accompanied by aberrantly increased expression of the Ink4a and Arf tumour suppressor genes...
  19. ncbi Arf-induced turnover of the nucleolar nucleophosmin-associated SUMO-2/3 protease Senp3
    Mei Ling Kuo
    Howard Hughes Medical Institute, Department of Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Cell Cycle 7:3378-87. 2008
    The stabilization and subcellular localization of the p19(Arf) tumor suppressor protein and the SUMO-2/3 deconjugating protease Senp3 each depend upon their binding to the abundant nucleolar protein nucleophosmin (Npm/B23)...
  20. ncbi The PTEN and INK4A/ARF tumor suppressors maintain myelolymphoid homeostasis and cooperate to constrain histiocytic sarcoma development in humans
    Daniel R Carrasco
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Cell 9:379-90. 2006
    ..Similarly, human HS showed genetic or epigenetic inactivation of PTEN, p16(INK4A), and p14(ARF), supporting the relevance of this genetically engineered mouse model of HS...
  21. ncbi Ink4a/Arf tumor suppressor does not modulate the degenerative conditions or tumor spectrum of the telomerase-deficient mouse
    Christine M Khoo
    Department of Medical Oncology, Belfer Foundation Institute for Innovative Cancer Science, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:3931-6. 2007
    The Rb/p16(Ink4a) and p53/p19Arf tumor suppressor pathways have been linked to diverse cancer-relevant processes, including those governing the cellular responses to telomere dysfunction...
  22. ncbi ROS fusion tyrosine kinase activates a SH2 domain-containing phosphatase-2/phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling axis to form glioblastoma in mice
    Al Charest
    Department of Biology and Center for Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Cancer Res 66:7473-81. 2006
    ..rearrangement product of ROS (FIG-ROS) cooperates with loss of the tumor suppressor gene locus Ink4a;Arf to produce glioblastomas in the mouse...
  23. ncbi The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells
    Adrian P Bracken
    Centre for Epigenetics, Biotech Research and Innovation Centre BRIC, University of Copenhagen, Copenhagen 2200, Denmark
    Genes Dev 21:525-30. 2007
    The p16INK4A and p14ARF proteins, encoded by the INK4A-ARF locus, are key regulators of cellular senescence, yet the mechanisms triggering their up-regulation are not well understood...
  24. ncbi Transcription factor E4F1 is essential for epidermal stem cell maintenance and skin homeostasis
    Matthieu Lacroix
    Institut de Genetique Moleculaire de Montpellier, UMR5535, Centre National de la Recherche Scientifique, 34293 Montpellier, France
    Proc Natl Acad Sci U S A 107:21076-81. 2010
    ..The clonogenic potential of E4F1 KO ESCs is rescued by Bmi1 overexpression or by Ink4a/Arf or p53 depletion...
  25. ncbi Role of the INK4a locus in tumor suppression and cell mortality
    M Serrano
    Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York, 11724 USA
    Cell 85:27-37. 1996
    The cell cycle inhibitor p16INK4a is inactivated in many human tumors and in families with hereditary melanoma and pancreatic cancer...
  26. ncbi Inactivation of TIF1gamma cooperates with Kras to induce cystic tumors of the pancreas
    David F Vincent
    INSERM, U590, IFR62, Lyon, France
    PLoS Genet 5:e1000575. 2009
    ....
  27. ncbi Modeling INK4/ARF tumor suppression in the mouse
    Justin H Berger
    Massachusetts General Hospital Cancer Center, Department of Medicine, Harvard Medical School, Boston, MA 02114, USA
    Curr Mol Med 7:63-75. 2007
    The INK4/ARF locus encodes the p15(INK4B), p16(INK4A) and p14(ARF) tumor suppressor proteins whose loss of function is associated with the pathogenesis of many human cancers...
  28. ncbi Impaired processing of DNA photoproducts and ultraviolet hypermutability with loss of p16INK4a or p19ARF
    Papri Sarkar-Agrawal
    Department of Dermatology, Boston University School of Medicine, Boston, MA 02118, USA
    J Natl Cancer Inst 96:1790-3. 2004
    ..We transfected unirradiated mouse fibroblast cells with UV-treated DNA to measure DNA repair in normal, p16INK4a mutant, p19ARF mutant, or double mutant mouse host cells...
  29. ncbi Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF
    T Kamijo
    Howard Hughes Medical Institute, Department of Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Cell 91:649-59. 1997
    The INK4a tumor suppressor locus encodes p16INK4a, an inhibitor of cyclin D-dependent kinases, and p19ARF, an alternative reading frame protein that also blocks cell proliferation...
  30. ncbi Ink4a/Arf expression is a biomarker of aging
    Janakiraman Krishnamurthy
    Department of Medicine, The Lineberger Comprehensive Cancer Center, The University of North Carolina School of Medicine, Chapel Hill, North Carolina, 27599 7295, USA
    J Clin Invest 114:1299-307. 2004
    The Ink4a/Arf locus encodes 2 tumor suppressor molecules, p16INK4a and Arf, which are principal mediators of cellular senescence...
  31. ncbi Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing
    Anna V Molofsky
    Howard Hughes Medical Institute, Department of Internal Medicine, and Center for Stem Cell Biology, University of Michigan, Ann Arbor, Michigan 48109 2216, USA
    Nature 443:448-52. 2006
    ..These declines in progenitor frequency and function correlate with increased expression of p16INK4a, which encodes a cyclin-dependent kinase inhibitor linked to senescence...
  32. ncbi Mitochondrial p32 is a critical mediator of ARF-induced apoptosis
    Koji Itahana
    Department of Radiation Oncology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7512, USA
    Cancer Cell 13:542-53. 2008
    The shared exon 2 of the p14ARF-p16INK4a locus is frequently mutated in human cancers. However, in contrast to the exon 1beta-encoded N-terminal half of ARF, the function of the exon 2-encoded C-terminal half of ARF has been elusive...
  33. ncbi Ndy1/KDM2B immortalizes mouse embryonic fibroblasts by repressing the Ink4a/Arf locus
    Alexandros Tzatsos
    Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111, USA
    Proc Natl Acad Sci U S A 106:2641-6. 2009
    ..that Ndy1 is down-regulated during senescence in mouse embryonic fibroblasts (MEFs) and that it represses the Ink4a/Arf locus...
  34. ncbi Loss of p16Ink4a confers susceptibility to metastatic melanoma in mice
    P Krimpenfort
    Division of Molecular Genetics and Centre for Biomedical Genetics, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
    Nature 413:83-6. 2001
    ..However, because CDKN2A encodes two distinct cell cycle inhibitory proteins, p16INK4a and p14ARF (p19Arf in mice), the mechanism of tumour suppression by CDKN2A has remained controversial...
  35. ncbi Mice doubly deficient for the Polycomb Group genes Mel18 and Bmi1 reveal synergy and requirement for maintenance but not initiation of Hox gene expression
    T Akasaka
    Department of Molecular Embryology, Graduate School of Medicine, Chiba University, Chuo Ku, Chiba 260 8670, Japan
    Development 128:1587-97. 2001
    ..Furthermore, we show an unexpected requirement for Mel18 and Bmi1 gene products to maintain stable expression of Hox cluster genes in regions caudal to the prospective anterior expression boundaries during subsequent development...
  36. ncbi Association of p19(ARF) with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53
    R Honda
    School of Life Science, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, Tokyo 192 0392, Japan
    EMBO J 18:22-7. 1999
    ..We further investigated whether the tumor suppressor p19(ARF) affects the ubiquitin ligase activity of Mdm2 for p53...
  37. ncbi Polycomb complexes regulate cellular senescence by repression of ARF in cooperation with E2F3
    Jun Miki
    Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Nagano 390 8621, Japan
    Genes Cells 12:1371-82. 2007
    ..Mel18-null MEFs undergo typical premature senescence accompanied by the up-regulation of ARF/p53/p16(INK4a) and decrease of Ring1b/Bmi1...
  38. ncbi Tumour biology: Policing of oncogene activity by p53
    Alejo Efeyan
    Spanish National Cancer Centre (CNIO, Madrid 28029, Spain
    Nature 443:159. 2006
  39. ncbi Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1
    Atsushi Iwama
    Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, University of Tokyo, Tokyo 108 8639, Japan
    Immunity 21:843-51. 2004
    ..Our findings define Bmi-1 as a central player in HSC self-renewal and demonstrate that Bmi-1 is a target for therapeutic manipulation of HSCs...
  40. ncbi Nucleophosmin is required for DNA integrity and p19Arf protein stability
    Emanuela Colombo
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    Mol Cell Biol 25:8874-86. 2005
    Nucleophosmin (NPM) is a nucleolar phosphoprotein that binds the tumor suppressors p53 and p19(Arf) and is thought to be indispensable for ribogenesis, cell proliferation, and survival after DNA damage...
  41. ncbi A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy
    Clemens A Schmitt
    Cold Spring Harbor Laboratory, 1 Bungtown Road, New York 11724, USA
    Cell 109:335-46. 2002
    ..that primary murine lymphomas also respond to chemotherapy by engaging a senescence program controlled by p53 and p16(INK4a)...
  42. ncbi E1A signaling to p53 involves the p19(ARF) tumor suppressor
    E de Stanchina
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 USA
    Genes Dev 12:2434-42. 1998
    ..activates p53 through a signaling pathway involving the retinoblastoma protein and the tumor suppressor p19(ARF)...
  43. ncbi Both p16(Ink4a) and the p19(Arf)-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse
    Nabeel Bardeesy
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:5947-52. 2006
    Activating KRAS mutations and p16(Ink4a) inactivation are near universal events in human pancreatic ductal adenocarcinoma (PDAC)...
  44. ncbi Oncogenic activity of Cdc6 through repression of the INK4/ARF locus
    Susana Gonzalez
    Tumor Suppression Group, Spanish National Cancer Research Center CNIO, E 28029 Madrid, Spain
    Nature 440:702-6. 2006
    The INK4/ARF locus encodes three tumour suppressors (p15(INK4b), ARF and p16(INK4a)) and is among the most frequently inactivated loci in human cancer...
  45. ncbi Role of genomic instability and p53 in AID-induced c-myc-Igh translocations
    Almudena R Ramiro
    Laboratory of Molecular Immunology, The Rockefeller University, Universidad Autonoma de Madrid, Madrid 28049, Spain
    Nature 440:105-9. 2006
    ..In addition, translocations are inhibited by the tumour suppressors ATM, Nbs1, p19 (Arf) and p53, which is consistent with activation of DNA damage- and oncogenic stress-induced checkpoints during ..
  46. ncbi mTOR promotes survival and astrocytic characteristics induced by Pten/AKT signaling in glioblastoma
    Xiaoyi Hu
    Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Neoplasia 7:356-68. 2005
    ....
  47. ncbi Sumoylation induced by the Arf tumor suppressor: a p53-independent function
    Kenji Tago
    Howard Hughes Medical Institute, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Proc Natl Acad Sci U S A 102:7689-94. 2005
    The mouse p19(Arf) protein has both p53-dependent and p53-independent tumor-suppressive activities...
  48. ncbi Identification of candidate cancer-causing genes in mouse brain tumors by retroviral tagging
    Fredrik K Johansson
    Department of Genetics and Pathology, The Rudbeck Laboratory, University Hospital, SE 751 85 Uppsala, Sweden
    Proc Natl Acad Sci U S A 101:11334-7. 2004
    ..Our findings indicate that retroviral tagging with a growth factor-encoding virus may be a powerful means of identifying candidate tumor-causing genes in nonhematopoietic tumors...
  49. ncbi Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16(Ink4a)-p19(Arf) pathway
    Dmitry V Bulavin
    Gene Response Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Genet 36:343-50. 2004
    ..Disruption of the gene Cdkn2a (encoding p16 and p19), but not of Trp53 (encoding p53), reconstituted cell transformation in Ppm1d-null MEFs...
  50. ncbi ARF suppresses tumor angiogenesis through translational control of VEGFA mRNA
    Hiroyuki Kawagishi
    Department of Mechanism of Aging, National Center for Geriatrics and Gerontology, Aichi, Japan
    Cancer Res 70:4749-58. 2010
    ..Here, we report that the nucleolar tumor suppressor p19(ARF) suppresses VEGFA expression, acting at the level of mRNA translation without affecting the transcription of the ..
  51. ncbi Expression of the p16INK4a tumor suppressor versus other INK4 family members during mouse development and aging
    F Zindy
    Department of Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Oncogene 15:203-11. 1997
    ..Both p18INK4c and p19INK4d were widely expressed during mouse embryogenesis, but p16INK4a and p15INK4b were not readily detected prenatally...
  52. ncbi Prolonged activation of the mitogen-activated protein kinase pathway promotes DNA synthesis in primary hepatocytes from p21Cip-1/WAF1-null mice, but not in hepatocytes from p16INK4a-null mice
    K L Auer
    Department of Radiation Oncology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA
    Biochem J 336:551-60. 1998
    ..DNA synthesis and increased expression of the cyclin-dependent kinase inhibitor (CKI) proteins p21Cip-1/WAF1 and p16INK4a. To evaluate the relative importance of these CKIs in mediating this response, we determined the impact of ..
  53. ncbi Thymocyte proliferation induced by pre-T cell receptor signaling is maintained through polycomb gene product Bmi-1-mediated Cdkn2a repression
    Masaki Miyazaki
    Department of Immunology, Graduate School of Biomedical Science, Hiroshima University, 1 2 3 Kasumi, Minami Ku, Hiroshima 734 8551, Japan
    Immunity 28:231-45. 2008
    ..cells induced by pre-TCR signaling required the Polycomb group (PcG) gene product Bmi-1-mediated repression of Cdkn2A, and that p19Arf expression resulted in thymocyte cell death and inhibited the transition from CD4(-)CD8(-) (DN) ..
  54. ncbi Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis
    C M Eischen
    Department of Biochemistry, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Genes Dev 13:2658-69. 1999
    ..In cultured primary mouse embryo fibroblasts, c-Myc activates the p19(ARF)-Mdm2-p53 tumor suppressor pathway, enhancing p53-dependent apoptosis but ultimately selecting for surviving ..
  55. ncbi Differential p53-independent outcomes of p19(Arf) loss in oncogenesis
    Zhenbang Chen
    Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology, Harvard Medical School, Boston, MA 02115, USA
    Sci Signal 2:ra44. 2009
    One reported function of the tumor suppressor p19(Arf) is to stabilize p53, providing a critical checkpoint in the response to oncogenic insults...
  56. ncbi The Arf tumor suppressor gene promotes hyaloid vascular regression during mouse eye development
    Robyn N McKeller
    Department of Hematology Oncology, Developmental Neurobiology, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA
    Proc Natl Acad Sci U S A 99:3848-53. 2002
    A key tumor suppressor mechanism that is disrupted frequently in human cancer involves the ARF and p53 genes...
  57. ncbi Genome-wide retroviral insertional tagging of genes involved in cancer in Cdkn2a-deficient mice
    Anders H Lund
    Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
    Nat Genet 32:160-5. 2002
    ..for loci that can participate in tumorigenesis in collaboration with loss of the Cdkn2a-encoded tumor suppressors p16INK4a and p19ARF...
  58. ncbi Loss of p53 but not ARF accelerates medulloblastoma in mice heterozygous for patched
    C Wetmore
    Department of Developmental Neurobiology, St Jude Children s Research Hospital, Memphis, Tennessee 38105 2794, USA
    Cancer Res 61:513-6. 2001
    ..in tumor incidence was observed in Ptc+/- mice carrying a mutation in APC (Min+/-) or in Ptc+/- mice deficient in p19ARF. Thus, there is a specific interaction between p53 loss and heterozygosity of Ptc that results in medulloblastoma...
  59. ncbi Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation
    Anna V Molofsky
    Howard Hughes Medical Institute, and Departments of Internal Medicine and Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109 0934, USA
    Nature 425:962-7. 2003
    ..In the absence of Bmi-1, the cyclin-dependent kinase inhibitor gene p16Ink4a is upregulated in neural stem cells, reducing the rate of proliferation...
  60. ncbi Genetic determinants of malignancy in a mouse model for oligodendroglioma
    William A Weiss
    Department of Neurology, University of California, San Francisco, California 94143 0663, USA
    Cancer Res 63:1589-95. 2003
    Oligodendrogliomas of all grades overexpress epidermal growth factor receptor (EGFR), whereas deletion of ink4a/arf is found only in high-grade tumors...
  61. ncbi Transient expression of the Arf tumor suppressor during male germ cell and eye development in Arf-Cre reporter mice
    Adam Gromley
    Howard Hughes Medical Institute and Department of Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Proc Natl Acad Sci U S A 106:6285-90. 2009
    The Arf tumor suppressor is expressed transiently during mouse male germ cell and eye development...
  62. ncbi Cooperativity of p19ARF, Mdm2, and p53 in murine tumorigenesis
    Lynette Moore
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Oncogene 22:7831-7. 2003
    The p19ARF gene product responds to oncogenic stresses by interfering with the inhibitory effects of Mdm2 on p53, thus enhancing p53 activity and its antiproliferative functions...
  63. ncbi Dicer inactivation in osteoprogenitor cells compromises fetal survival and bone formation, while excision in differentiated osteoblasts increases bone mass in the adult mouse
    Tripti Gaur
    Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Dev Biol 340:10-21. 2010
    ..We propose that Dicer generated miRs are essential for two periods of bone formation, to promote osteoblast differentiation before birth, and control bone accrual in the adult...
  64. ncbi Characterization of melanoma cells capable of propagating tumors from a single cell
    Matthew A Held
    Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont, USA
    Cancer Res 70:388-97. 2010
    ..We anticipate that purification of these MPCs may allow a more comprehensive evaluation of the molecular features that define tumor-forming capability and chemotherapeutic resistance in melanoma...
  65. ncbi A novel type of cellular senescence that can be enhanced in mouse models and human tumor xenografts to suppress prostate tumorigenesis
    Andrea Alimonti
    Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 120:681-93. 2010
    ....
  66. ncbi Aging and cancer resistance in lymphoid progenitors are linked processes conferred by p16Ink4a and Arf
    Robert A J Signer
    Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA
    Genes Dev 22:3115-20. 2008
    ..These effects are due in part to the preferential expression of p16(Ink4a) and Arf in aged lymphoid progenitors...
  67. ncbi The Janus kinase 2 is required for expression and nuclear accumulation of cyclin D1 in proliferating mammary epithelial cells
    Kazuhito Sakamoto
    Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, Nebraska 68198 6805, USA
    Mol Endocrinol 21:1877-92. 2007
    ....
  68. ncbi The leukemia-associated cytoplasmic nucleophosmin mutant is an oncogene with paradoxical functions: Arf inactivation and induction of cellular senescence
    K Cheng
    Cancer Biology and Genetics Program, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Oncogene 26:7391-400. 2007
    ..We demonstrate that NPMc+ blocks the p19(Arf) (Arf) induction elicited by E1A...
  69. ncbi Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing p16Ink4a and p19Arf Expression
    Jinsuke Nishino
    Howard Hughes Medical Institute, Life Sciences Institute, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109 2216, USA
    Cell 135:227-39. 2008
    ..Self-renewal capacity declines with age, partly because of increasing expression of the tumor suppressor p16(Ink4a)...
  70. ncbi Wnt4 is not sufficient to induce lobuloalveolar mammary development
    Young Chul Kim
    McArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin Madison, Wisconsin, USA
    BMC Dev Biol 9:55. 2009
    ..Therefore, we generated conditional transgenic mice to test whether Wnt4 can stimulate mammary epithelial cell growth...
  71. ncbi The yin and yang of the Cdkn2a locus in senescence and aging
    Darren J Baker
    Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Cell Cycle 7:2795-802. 2008
    Senescence of cultured cells involves activation of the p19(Arf)-p53 and the p16(Ink4a)-Rb tumor suppressor pathways...
  72. ncbi IGFBP2 is a candidate biomarker for Ink4a-Arf status and a therapeutic target for high-grade gliomas
    Lynette M Moore
    Departments of Pathology and Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 106:16675-9. 2009
    ..Instead, absence of Ink4a-Arf resulted in elevated endogenous tumor cell IGFBP2. An inverse relationship between p16(INK4a) and IGFBP2 expression was also observed in human glioma tissue samples and in 90 different cancer cell lines ..
  73. ncbi Changes in p19Arf localization accompany apoptotic crisis during pre-B-cell transformation by Abelson murine leukemia virus
    Rebekah Stackpole Zimmerman
    Department of Pathology, Genetics Graduate Program, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Virol 82:8383-91. 2008
    ..process in which growth-stimulatory signals from the v-Abl oncoprotein and growth-suppressive signals from the p19(Arf)-p53 tumor suppressor pathway oppose each other and influence the outcome of infection...
  74. ncbi Genetic events and the role of TGF beta in epithelial tumour progression
    R J Akhurst
    Onyx Pharmaceuticals, Richmond, CA 94806, USA
    J Pathol 187:82-90. 1999
    ..It is this latter effect which may be clinically more significant, since many human tumours overexpress TGF beta, yet the majority still retain the intracellular signaling systems necessary for the cell to respond to this growth factor...
  75. ncbi Large-scale mutagenesis in p19(ARF)- and p53-deficient mice identifies cancer genes and their collaborative networks
    Anthony G Uren
    Division of Molecular Genetics and Cancer Genomics Centre, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands
    Cell 133:727-41. 2008
    p53 and p19(ARF) are tumor suppressors frequently mutated in human tumors...
  76. ncbi A conditional mouse model for malignant mesothelioma
    Johan Jongsma
    Department of Molecular Genetics, Cancer Genomics Centre, Centre for Biomedical Genetics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Cancer Cell 13:261-71. 2008
    ..Mesothelioma developed at high incidence in Nf2;Ink4a/Arf and Nf2;p53 conditional knockout mice with median survival times of approximately 30 and 20 weeks, respectively...
  77. ncbi The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence
    Karl Agger
    Biotech Research and Innovation Centre BRIC and Centre for Epigenetics, University of Copenhagen, DK 2200 Copenhagen, Denmark
    Genes Dev 23:1171-6. 2009
    The tumor suppressor proteins p16INK4A and p14ARF, encoded by the INK4A-ARF locus, are key regulators of cellular senescence...
  78. ncbi A gene expression signature associated with "K-Ras addiction" reveals regulators of EMT and tumor cell survival
    Anurag Singh
    Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94306, USA
    Cancer Cell 15:489-500. 2009
    ..These findings indicate that epithelial differentiation and tumor cell viability are associated, and that EMT regulators in "K-Ras-addicted" cancers represent candidate therapeutic targets...
  79. ncbi Bmi1 controls tumor development in an Ink4a/Arf-independent manner in a mouse model for glioma
    Sophia W M Bruggeman
    Division of Molecular Genetics, The Netherlands Cancer Institute, 1066CX, Amsterdam, The Netherlands
    Cancer Cell 12:328-41. 2007
    ..Repression of the Ink4a/Arf locus is a well described mechanism through which Bmi1 can exert its proliferative effects...
  80. ncbi Older age and dietary folate are determinants of genomic and p16-specific DNA methylation in mouse colon
    Mary K Keyes
    Vitamins and Carcinogenesis Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02478, USA
    J Nutr 137:1713-7. 2007
    ..Genomic DNA methylation and p16 promoter methylation in the colonic mucosa were analyzed by liquid chromatography/electrospray ionization/MS and ..
  81. ncbi Identification of tumor-initiating cells in a highly aggressive brain tumor using promoter activity of nucleostemin
    Akira Tamase
    Division of Molecular Genetics, Center for Cancer and Stem Cell Research, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920 0934, Japan
    Proc Natl Acad Sci U S A 106:17163-8. 2009
    ..drives GFP expression (termed NS-GFP) with a mouse brain tumor model induced by retroviral Ras expression on a p16(Ink4a)/p19(Arf)-deficient background...
  82. ncbi Identification of PDE4D as a proliferation promoting factor in prostate cancer using a Sleeping Beauty transposon-based somatic mutagenesis screen
    Eric P Rahrmann
    Department of Genetics, Cell Biology, and Development and Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA
    Cancer Res 69:4388-97. 2009
    ..These data indicate that PDE4D functions as a proliferation promoting factor in prostate cancer, and the Sleeping Beauty transposon system is a useful tool for identifying candidate prostate cancer genes...
  83. ncbi The biologic properties of leukemias arising from BCR/ABL-mediated transformation vary as a function of developmental origin and activity of the p19ARF gene
    Pin Yi Wang
    Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, NY, USA
    Blood 112:4184-92. 2008
    ..We have examined the role of the tumor suppressor gene p19(ARF) in a murine model of acute lymphoblastic leukemia and found that loss of p19(ARF) changes the spectrum of cells ..
  84. ncbi A head holder for magnetic resonance imaging that allows the stereotaxic alignment of spontaneously occurring intracranial mouse tumors
    Tsuyoshi Tada
    Department of Neurological Surgery, Preuss Laboratory of Molecular Neuro Oncology, Brain Tumor Research Center, University of California San Francisco, San Francisco, CA 94143 0520, USA
    J Neurosci Methods 116:1-7. 2002
    ..This allowed the precise localization of the tumor in all three dimensions. The strategy we employed is adaptable to other imaging modalities and to other body sites...
  85. ncbi Loss of Bax alters tumor spectrum and tumor numbers in ARF-deficient mice
    Christine M Eischen
    Department of Biochemistry, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Cancer Res 62:2184-91. 2002
    p19(ARF) is a key regulator of the p53-mediated apoptotic and tumor suppressor pathway...
  86. ncbi Senescence: a companion in chemotherapy?
    Anton Berns
    Division of Molecular Genetics and Centre of Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Cancer Cell 1:309-11. 2002
    ..Mouse lymphoma model points to an unsuspected role of drug-induced "senescence."..
  87. ncbi CARF is a novel protein that cooperates with mouse p19ARF (human p14ARF) in activating p53
    Md Kamrul Hasan
    Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology AIST, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8566, Japan
    J Biol Chem 277:37765-70. 2002
    The INK4a locus on chromosome 9p21 encodes two structurally distinct tumor suppressor proteins, p16(INK4a) and the alternative reading frame protein, ARF (p19(ARF) in mouse and p14(ARF) in human)...
  88. ncbi A strong candidate gene for the Papg1 locus on mouse chromosome 4 affecting lung tumor progression
    Zhongqiu Zhang
    Division of Human Cancer Genetics, The Ohio State University Comprehensive Cancer Center, 420 West 12th Avenue, Columbus 43210, USA
    Oncogene 21:5960-6. 2002
    ..This locus contains a candidate gene, Cdkn2a also referred to as Ink4a/Arf, which dually encodes two established tumor suppressors p16(INK4a) and ARF...
  89. ncbi Loss of p16INK4a results in increased glucocorticoid receptor activity during fibrosarcoma development
    Ramon Roca
    The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, 273 Fulham Road, London SW3 6JB, United Kingdom
    Proc Natl Acad Sci U S A 100:3113-8. 2003
    ..The cyclin-dependent kinase inhibitor p16(INK4a) is frequently absent in many cancers, including FSs...
  90. ncbi Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells
    In Kyung Park
    Division of Hematology Oncology, Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA
    Nature 423:302-5. 2003
    ..cell associated genes, cell survival genes, transcription factors, and genes modulating proliferation including p16Ink4a and p19Arf was altered in bone marrow cells of the Bmi-1-/- mice...
  91. ncbi Transcriptional coactivator Cited2 induces Bmi1 and Mel18 and controls fibroblast proliferation via Ink4a/ARF
    Kamil R Kranc
    Department of Cardiovascular Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
    Mol Cell Biol 23:7658-66. 2003
    ..in growth fraction, senescent cellular morphology, and increased expression of the cell proliferation inhibitors p16(INK4a), p19(ARF), and p15(INK4b)...
  92. ncbi Cdk6-cyclin D3 activity in murine ES cells is resistant to inhibition by p16(INK4a)
    Renate Faast
    Department of Molecular Biosciences, BresaGen Cell Therapy Program, Center for Molecular Genetics of Development, University of Adelaide, Adelaide, South Australia, Australia
    Oncogene 23:491-502. 2004
    ..To investigate the basis underlying the insensitivity of ES cells to ectopic p16 expression, we show that Cdk6-cyclin D3 complexes are not subject to inhibition by p16, similar to Cdk-viral cyclin ..
  93. ncbi Transgenic expression of the p16(INK4a) cyclin-dependent kinase inhibitor leads to enhanced apoptosis and differentiation arrest of CD4-CD8- immature thymocytes
    Chantal Lagresle
    Institut National de la Sante et de la Recherche Medicale, Unite 462, Laboratoire 10, Ligue Nationale Contre le Cancer, Institut Universitaire d Hematologie, Hopital Saint Louis, 1 avenue Claude Vellefaux, 75475 Paris Cedex 10, France
    J Immunol 168:2325-31. 2002
    ..Deletion of the cell cycle inhibitor p16(INK4a) is frequently observed in human T cell neoplasias and, in mice, gene targeted inactivation of the Ink4a ..
  94. ncbi Regulation of cyclin D1 and p16(INK4A) is critical for growth arrest during mammary involution
    M Gadd
    Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129, USA
    Cancer Res 61:8811-9. 2001
    ..Here we report that the arrest involves a unique pulse of p16(INK4A) expression in vivo, which accompanies decreased cyclin D1 expression and a shift to an active repressor E2F4 ..
  95. ncbi Identification of the gene immediately downstream of the murine INK4a/ARF locus
    C Pantoja
    Department of Immunology and Oncology, National Center of Biotechnology, Campus de Cantoblanco, Madrid E 28049, Spain
    Exp Gerontol 36:1289-302. 2001
    ..the 3'-terminal exon of the gene immediately downstream of the INK4a/ARF locus, which we have called NTp16 (Next-To-p16)...
  96. ncbi Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest
    D E Quelle
    Howard Hughes Medical Institute, St Jude Children s Research Hospital, Memphis, Tennessee 38101, USA
    Cell 83:993-1000. 1995
    The INK4a (MTS1, CDKN2) gene encodes an inhibitor (p16INK4a) of the cyclin D-dependent kinases CDK4 and CDK6 that blocks them from phosphorylating the retinoblastoma protein (pRB) and prevents exit from the G1 phase of the cell cycle...
  97. ncbi Frequent aberrant methylation of p16INK4a in primary rat lung tumors
    D S Swafford
    Inhalation Toxicology Research Institute, Albuquerque, New Mexico 87185, USA
    Mol Cell Biol 17:1366-74. 1997
    The p16INK4a (p16) tumor suppressor gene is frequently inactivated by homozygous deletion or methylation of the 5' CpG island in cell lines derived from human non-small-cell lung cancers...
  98. ncbi Accumulation of p16INK4a in mouse fibroblasts as a function of replicative senescence and not of retinoblastoma gene status
    I Palmero
    Molecular Oncology Laboratory, Imperial Cancer Research Fund, London, UK
    Oncogene 15:495-503. 1997
    ..no cyclin D1-Cdk4 complexes can be detected because all the available Cdk4 is associated with the Cdk-inhibitor p16INK4a. In contrast, SV40-transformed mouse cells and fibroblasts from Rh1-nullizygous mouse embryos contain normal ..
  99. ncbi Mouse models in tumor suppression
    N Ghebranious
    Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Oncogene 17:3385-400. 1998
    ..In this review, we discuss some of the mechanistic insights provided by tumor suppressor-deficient mice and their utility as models for human cancer syndromes...
  100. ncbi Short dysfunctional telomeres impair tumorigenesis in the INK4a(delta2/3) cancer-prone mouse
    R A Greenberg
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Cell 97:515-25. 1999
    ..The results described here demonstrate that loss of telomere function in a cancer-prone mouse model possessing intact DNA damage responses impairs, but does not prevent, tumor formation...
  101. ncbi Involvement of the Ink4a gene (p16 and p19arf) in murine tumorigenesis
    I Orlow
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Int J Oncol 15:17-24. 1999
    The INK4A and INK4B genes map to 9p21, with the INK4A gene encoding two products, p16 and p19ARF. Many neoplasms in which INK4A and INK4B genes are altered show deletions involving both genes...

Research Grants50

  1. Molecular dissection of pancreatic ductal adenocarcinoma
    Brian Lewis; Fiscal Year: 2009
    ..Such gene expression signatures may potentially be used as diagnostic tools, as well as surrogate markers for response to targeted therapeutic interventions. ..
  2. Mouse Model of Pancreatic Cancer Progression-Maintenance
    Nabeel Bardeesy; Fiscal Year: 2007
    Activating mutations of KRAS and losses of INK4a/ARF are thought to occur at the early stages of pancreatic adenocarcinoma pathogenesis while losses of p53 and SMAD4 are associated with the emergence of more advanced lesions...
  3. Melanoma in p16INK4a and p19ARF Deficient Mice
    NORMAN SHARPLESS; Fiscal Year: 2006
    ..The Ink4a/Arf locus, conserved in mouse and humans, encodes two distinct proteins, p16INK4a and p19ARF, both of which regulate critical tumor suppressor pathways, and each may play a substantive role in ..
  4. Molecular mediators of metastasis in hepatocellular carcinoma
    Brian Lewis; Fiscal Year: 2009
    ..findings, we propose to: 1) Explore whether the induction of metastasis is dependent on the loss of either the p16 or p19 tumor suppressor proteins (encoded by the Ink4a/Arf locus), or both...
  5. The role of p16INK4a in mammalian aging
    NORMAN SHARPLESS; Fiscal Year: 2007
    ..As the only known function of p16INK4a is to induce cell cycle arrest, this increased p16 INK4a expression may play a significant role in the impaired tissue regeneration and stem cell function characteristic ..
  6. Molecular mediators of metastasis in hepatocellular carcinoma
    Brian Lewis; Fiscal Year: 2007
    ..findings, we propose to: 1) Explore whether the induction of metastasis is dependent on the loss of either the p16 or p19 tumor suppressor proteins (encoded by the Ink4a/Arf locus), or both...
  7. A flexible somatic and sporadic mouse model for pancreatic ductal adenocarcinoma
    Brian Lewis; Fiscal Year: 2007
    ..Such an advance would benefit public health by reducing the mortality associated with this disease. ..
  8. The role of p16INK4a in mammalian aging
    Norman Edward Sharpless; Fiscal Year: 2010
    Work, from our lab and others, has established that the beneficial, anti-cancer function of the p16INK4a tumor suppressor mechanism also untowardly contributes to mammalian aging...
  9. Molecular dissection of pancreatic ductal adenocarcinoma
    Brian Lewis; Fiscal Year: 2009
    ..Such gene expression signatures may potentially be used as diagnostic tools, as well as surrogate markers for response to targeted therapeutic interventions. ..
  10. Molecular dissection of pancreatic ductal adenocarcinoma
    Brian C Lewis; Fiscal Year: 2010
    ..Such gene expression signatures may potentially be used as diagnostic tools, as well as surrogate markers for response to targeted therapeutic interventions. ..
  11. Molecular mediators of metastasis in hepatocellular carcinoma
    Brian C Lewis; Fiscal Year: 2010
    ..findings, we propose to: 1) Explore whether the induction of metastasis is dependent on the loss of either the p16 or p19 tumor suppressor proteins (encoded by the Ink4a/Arf locus), or both...
  12. Molecular dissection of pancreatic ductal adenocarcinoma
    Brian C Lewis; Fiscal Year: 2010
    ..Such gene expression signatures may potentially be used as diagnostic tools, as well as surrogate markers for response to targeted therapeutic interventions. ..
  13. Genome-wide Analysis of Aging in Yeast
    Brian Kennedy; Fiscal Year: 2009
    ..When completed, this study will dramatically improve our understanding of aging in yeast and lead to models of caloric restriction that can be tested in mammalian systems. ..
  14. The genetic Basis of Melanoma Metastasis
    Lynda Chin; Fiscal Year: 2010
    ..pursue the validation of new metastasis candidates through low-complexity in vivo genetic screens followed by rigorous functional and clinical validation in human melanoma cells and melanoma specimen on TMA, respectively ..
  15. TOR, Translation and Aging
    Brian Kennedy; Fiscal Year: 2009
    ..Through achieving a better understand of the modulatory role played by regulated protein translation in aging, we will be able to pinpoint key targets for pharmacological interventions. ..
  16. Nuclear Lamin Functions and Human Disease
    Brian Kennedy; Fiscal Year: 2009
    ..Findings from these studies will identify and test potential mechanistic underpinnings that underlie Hutchinson-Gilford progeria syndrome and other A-type lamin-associated diseases. ..
  17. S6 Kinase, Aging and Age-related Disease
    Brian Kennedy; Fiscal Year: 2009
    ..We have determined that reduced S6 kinase function leads to lifespan extension in organisms ranging from yeast to mice. In this proposal, we will dissect the mechanisms by which S6 kinase activity accelerates the aging process. ..
  18. MOLECULAR PATHOGENESIS OF MALIGNANT MELANOMA
    Lynda Chin; Fiscal Year: 2002
    ..Specifically, I will focus on the differential roles of p15 INK4b, P16INK4a and p19ARF as well as activated H-rasva112 in development of malignant melanoma...
  19. MET Activation in Melanoma Genesis and Progression
    Lynda Chin; Fiscal Year: 2006
    ..will be examined on phenotypic, molecular/genetic and genomic levels to validate a role for MET in progression, and ultimately to delineate genes and pathways critically important for tumor progression, and possibly metastasis ..
  20. Genomic & Genetic Characterization of Amplicons in GBMs
    Lynda Chin; Fiscal Year: 2007
    ..The highest potential candidate glioma oncogene will be further validated by rigorous in vivo transgenesis study. ..
  21. Genome-wide Analysis of Aging in Yeast
    Brian Kennedy; Fiscal Year: 2007
    ..When completed, this study will dramatically improve our understanding of aging in yeast and lead to models of caloric restriction that can be tested in mammalian systems. ..
  22. Nuclear Lamin Functions and Human Disease
    Brian Kennedy; Fiscal Year: 2007
    ..Myoblast cell lines, generated from Lmna-/- mice, exhibit differentiation defects. These defects will be studied at the molecular level to better understand how aberrant A-type lamin function leads to tissue degeneration. ..
  23. The genetic Basis of Melanoma Metastasis
    Lynda Chin; Fiscal Year: 2007
    ....