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Abnormalities in Cell Cycle Control in Human Cancer and Their Relevance to Chemoprevention

  • Chapter
Cancer Chemoprevention

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Carcinogenesis is a multistep process characterized by the progressive acquisition of mutations and epigenetic abnormalities in expression of a variety of cellular genes, which eventually leads to the appearance of a fully malignant cancer. The genes involved in the carcinogenic process have been subdivided into two major categories: oncogenes, dominant-acting genes with increased activity that contributes to tumor development; and tumor-suppressor genes, recessive-acting genes whose functional loss enhances tumor development (1, 2). These genes have highly diverse functions, and contribute to cancer formation through multiple mechanisms. Intracellular pathways are involved in signal transduction and gene expression, cell-cycle control, DNA repair and genomic stability, and cell-fate determination-e.g., differentiation, senescence, and apoptosis. Extracellular pathways to cancer formation include tumor invasion, metastasis, and angiogenesis.

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References

  1. Fearon ER. Tumor suppressor genes, in The Genetic Basis of Human Cancer Vogelstein B, Kinzler KW, eds. McGraw-Hill, New York, NY, 1998, pp.229–236.

    Google Scholar 

  2. Park M. Oncogenesis, in The Genetic Basis of Human Cancer. Vogelstein B, Kinzler KW, eds. McGraw-Hill, New York, NY, 1998, pp.205–228.

    Google Scholar 

  3. Lee MH, Yang HY. Negative regulators of cyclin-dependent kinases and their roles in cancers. Cell Mol Life Sci 2001;58:1907–1922.

    Article  PubMed  CAS  Google Scholar 

  4. Sgambato A, Cittadini A, Faraglia B, Weinstein IB. Multiple functions of p27Kipl and its alterations in tumor cells: a review. JCell Physiol 2000;183:18–27.

    Article  CAS  Google Scholar 

  5. Sgambato A, Flamini G, Cittadini A, Weinstein IB. Abnormalities in cell cycle control in cancer and their clinical implications. Tumori 1998;84:421–433.

    PubMed  CAS  Google Scholar 

  6. Sherr CJ, Roberts JM. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dey 1999;13:1501–1512.

    Article  CAS  Google Scholar 

  7. Weinstein IB, Zhou P. Defects in cell cycle control genes in human cancern, in Encyclopedia of Cancer, Vol. 1. Bertino JR, ed. Academic Press, New York, NY, 1997, pp.256–267.

    Google Scholar 

  8. Weinstein IB. Disorders in cell circuitry during multistage carcinogenesis: the role of homeostatis. Carcinogenesis 2000;21:857–864.

    Article  PubMed  CAS  Google Scholar 

  9. Pardee AB. G1 events and regulation of cell proliferation. Science 1989;246:603–608.

    Article  PubMed  CAS  Google Scholar 

  10. Sherr CJ. D-type cyclins. Trends Biochem Sci 1995;20:187–190.

    Article  PubMed  CAS  Google Scholar 

  11. Draetta GF. Mammalian G1 cyclins. Curr Opin Cell Biol 1994;6:842–846.

    Article  PubMed  CAS  Google Scholar 

  12. Shen CJ, Roberts JM. Inhibitors of mammalian G1 cyclindependent kinases. Genes Dev 1995;9:1149–1163.

    Article  Google Scholar 

  13. Carrano AC, Eytan E, Hershko A, Pagano, M. SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27Kipl. Nat Cell Biol 1999;1:193–199.

    Article  PubMed  CAS  Google Scholar 

  14. Hara T, Kamura T, Nakayama K, et al. Degradation of p27Kipl at the G0-G1 transition mediated by a Skp2-independent ubiquination pathway. J Biol Chem 2001;276:48,

    Google Scholar 

  15. Hara T, Kamura T, Nakayama K, et al. Degradation of p27Kipl at the G0-G1 transition mediated by a Skp2-independent ubiquination pathway. J Biol Chem 2001;276: 937–48,

    Article  Google Scholar 

  16. Hara T, Kamura T, Nakayama K, et al. Degradation of p27Kipl at the G0-G1 transition mediated by a Skp2-independent ubiquination pathway. J Biol Chem 2001;276: 943.

    Google Scholar 

  17. LaBaer J, Garrett MD, Stevenson LF, et al. New functional activities for the p21 family of CDK inhibitors. Genes Dev 1997;11:847–862.

    Article  PubMed  CAS  Google Scholar 

  18. Davezac N, Baldin V, Gabrielli B, et al. Regulation of CDC25B phosphatases subcellular localization. Oncogene 2000;19:2179–2185.

    Article  PubMed  CAS  Google Scholar 

  19. Weinberg RA. The retinoblastoma protein and cell cycle control. Cell 1995;81:323–330.

    Article  PubMed  CAS  Google Scholar 

  20. Nevins JR. The Rb/E2F pathway and cancer. Hum Mol Genet 2001;10:699–703.

    Article  PubMed  CAS  Google Scholar 

  21. Lin HM, Zhao L, Cheng SY. Cyclin D1 is a ligandindependent co-repressor for thyroid hormone receptors. J Biol Chem 2002;277:28,733–28,741.

    Google Scholar 

  22. Lin HM, Zhao L, Cheng SY. Cyclin D1 is a ligandindependent co-repressor for thyroid hormone receptors. J Biol Chem 2002;277: 733–28,

    Google Scholar 

  23. Lin HM, Zhao L, Cheng SY. Cyclin D1 is a ligandindependent co-repressor for thyroid hormone receptors. J Biol Chem 2002;277: 741.

    Google Scholar 

  24. Reutens AT, Fu M, Wang C, et al. Cyclin D1 binds the androgen receptor and regulates hormone-dependent signaling in a p300/CBP-associated factor (P/CAF)-dependent manner. Mol Endocrinol 2001;15:797–811.

    Article  PubMed  CAS  Google Scholar 

  25. Zwijsen RM, Wientjens E, Klompmaker R, et al. CDK-independent activation of estrogen receptor by cyclin D1. Cell 1997;88:405–415.

    Article  PubMed  CAS  Google Scholar 

  26. Yao Y, Doki Y, Jiang W, et al. Cloning and characterization of DIP 1, a novel protein that is related to the Id family of proteins. Exp Cell Res 2000;257:22–32.

    Article  PubMed  CAS  Google Scholar 

  27. Ozbun MA, Butel JS. P53 tumor suppressor gene: structure and function, in Encyclopedia of Cancer, Vol. 2. Bertino JR, ed. Academic Press, New York, NY, 1997, pp.1240–1257.

    Google Scholar 

  28. Aktas H, Cai H, Cooper GM. Ras links growth factor signaling to the cell cycle machinery via regulation of cyclin D1 and the Cdk inhibitor p27Kipl. Mol Cell Biol 1997;17:3850–3857.

    PubMed  CAS  Google Scholar 

  29. Joyce, D., Albanese, C., Steer, J., et al. NF-KB and cell-cycle regulation: the cyclin connection. Cytokine Growth Factor Rev 2001;12:73–90.

    Article  PubMed  CAS  Google Scholar 

  30. Smalley MJ, Dale TC. Wnt signalling in mammalian development and cancer. Cancer Metastasis Rev 1999;18:215–230.

    Article  PubMed  CAS  Google Scholar 

  31. Turkson J, Jove R. STAT proteins: novel molecular targets for cancer drug discovery. Oncogene 2000;19:6613–6626.

    Article  PubMed  CAS  Google Scholar 

  32. Grandori C, Cowley SM, James LP, Eisenman RN. The Myc/Max/Mad network and the transcriptional control of cell behavior. Annu Rev Cell Dev Biol 2000;16:653–699.

    Article  PubMed  CAS  Google Scholar 

  33. Jiang W, Kahn SM, Zhou P, et al. Overexpression of cyclin D1 in rat fibroblasts causes abnormalities in growth control, cell cycle progression and gene expression. Oncogene 1993;8:3447–3457.

    PubMed  CAS  Google Scholar 

  34. Opitz OG, Suliman Y, Hahn WC, et al. Cyclin D1 overexpression and p53 inactivation immortalize primary oral keratinocytes by a telomerase-independent mechanism. J Clin Investig 2001;108:725–732.

    PubMed  CAS  Google Scholar 

  35. Fantl V, Stamp G, Andrews A, et al. Mice lacking cyclin D1 are small and show defects in eye and mammary gland development. Genes Dev 1995;9:2364–2372.

    Article  PubMed  CAS  Google Scholar 

  36. Zhou P, Jiang W, Weghorst CM, Weinstein IB. Overexpression of cyclin D1 enhances gene amplification. Cancer Res 1996;56:36–39.

    PubMed  CAS  Google Scholar 

  37. Bartkova J, Lukas J, Muller H, et al. Cyclin D1 protein expression and function in human breast cancer. Int J Cancer 1994;57:353–361.

    Article  PubMed  CAS  Google Scholar 

  38. Jiang W, Zhang Y- J, Kahn SM, et al. Altered expression of the cyclin D1 and retinoblastoma genes in human esophageal cancer. Proc Natl Acad Sci USA 1993;90:9026–9030.

    Article  PubMed  CAS  Google Scholar 

  39. Bortner DM, Rosenberg MP. Induction of mammary gland hyperplasia and carcinomas in transgenic mice expressing human cyclin E. Mol Cell Biol 1997;17:453–459.

    CAS  Google Scholar 

  40. Strohmaier H, Spruck CH, Kaiser P, et al. Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line. Nature 2001;413:316–322.

    CAS  Google Scholar 

  41. Sherr CJ. Tumor surveillance via the ARF-p53 pathway. Genes Dev 1998;12:2984–2991.

    Article  PubMed  CAS  Google Scholar 

  42. Mammilapalli R, Gavrilova N, Mihaylova VT, et al. PTEN regulates the ubiquitin-dependent degradation of the cdk inhibitor p27kip 1 through the ubiquitin 3 ligase SCF (SKP2). Curr Biol 2001;11:263–267.

    Article  Google Scholar 

  43. Soucek T, Yeung RS, Hengstschlager M. Inactivation of the cyclin-dependent kinase inhibitor p27 upon loss of the tuberous sclerosis complex gene-2. Proc Natl Acad Sci USA 1998;95:15

    Article  Google Scholar 

  44. Soucek T, Yeung RS, Hengstschlager M. Inactivation of the cyclin-dependent kinase inhibitor p27 upon loss of the tuberous sclerosis complex gene-2. Proc Natl Acad Sci USA 1998;95: 653–15,

    Article  Google Scholar 

  45. Soucek T, Yeung RS, Hengstschlager M. Inactivation of the cyclin-dependent kinase inhibitor p27 upon loss of the tuberous sclerosis complex gene-2. Proc Natl Acad Sci USA 1998;95: 658.

    Article  Google Scholar 

  46. Yao Y, Slosberg ED, Wang L, et al. Increased susceptibility to carcinogen-induced mammary tumors in MMTV Cdc25B transgenic mice. Oncogene 1999;18:5159–5166.

    Article  PubMed  CAS  Google Scholar 

  47. Pagliuca A, Gallo P, De Luca P, Lania L. Class A helixloop-helix proteins are positive regulators of several cyclin-dependent kinase inhibitors’ promoter activity and negatively affect cell growth. Cancer Res 2000;60:1376–1382.

    PubMed  CAS  Google Scholar 

  48. Tetsu O, McCormick F. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature (London) 1999;398:422–426.

    Article  CAS  Google Scholar 

  49. Arber N, Hibshoosh H, Moss SF, et al. Increased expression of cyclin D1 is an early event in multistage colorectal carcinogenesiss. Gastroenterology 1996;110:669–674.

    Article  PubMed  CAS  Google Scholar 

  50. Arber N, Lightdale C, Rotterdam H, et al. Increased expression of the cyclin D1 gene in Barrett’s esophagus. Cancer Epidemiol Biomarkers Prey 1996;5:457–459.

    CAS  Google Scholar 

  51. Brambilla E, Gazzeri S, Moro D, et al. Alterations of the Rb pathway (Rb-p 16INK4-cyclin D1) in preinvasive bronchial lesions. Clin Cancer Res 1999;5:243–250.

    PubMed  CAS  Google Scholar 

  52. Weinstat-Saslow D, Merino MJ, Manrow RE, et al. Overexpression of cyclin D1 mRNA distinguishes invasive and in situ breast carcinomas from non-malignant lesions. Nat Med 1995;1:1257–1260.

    Article  PubMed  CAS  Google Scholar 

  53. Keyomarsi K, Tucker SL, Buchholz TA, et al. Cyclin E and survival in patients with breast cancer. N Engl J Med 2002;347:1566–1575

    Article  PubMed  CAS  Google Scholar 

  54. Yu M, Zhan Q, Finn OJ. Immune recognition of cyclin B1 as a tumor antigen is a result of its overexpression in human tumors that is caused by non-functional p53. Mol Immunol 2001;38:981–987.

    Article  Google Scholar 

  55. Soria JC, Jang SJ, Khuri FR, et al. Overexpression of cyclin B1 in early-stage non-small cell lung cancer and its clinical implication. Cancer Res 2000;60:4000–4004.

    PubMed  CAS  Google Scholar 

  56. Sarafan-Vasseur N, Lamy A, Bourguignon J, et al. Overexpression of B-type cyclins alters chromosomal segregation. Oncogene 2002;21:2051–2057.

    Article  PubMed  CAS  Google Scholar 

  57. Soria JC, Rodriguez M, Liu DD, et al. Aberrant promoter methylation of multiple genes in bronchial brush samples from former cigarette smokers. Cancer Res 2002;62:351–355.

    PubMed  CAS  Google Scholar 

  58. Orend G, Hunter T, Ruoslahti E. Cytoplasmic displacement of cyclin E-cdk2 inhibitors p21 ciP 1 and p27kiP 1 in anchorageindependent cells. Oncogene 1998;16:2575–2583.

    Article  PubMed  CAS  Google Scholar 

  59. Singh SP, Lipman J, Goldman H, et al. Loss or altered subcellular localization of p27 in Barrett’s associated adenocarcinomas. Cancer Res 1998;58:1730–1735.

    PubMed  CAS  Google Scholar 

  60. Blain SW, Massaguè J. Breast cancer banishes p27 from the nucleus Nat Med 2002;8:1076–1078.

    Article  PubMed  CAS  Google Scholar 

  61. Blagosklonny MV. Are p27 and p21 cyctoplasmic oncoproteins? Cell Cycle 2002;1:391–393.

    Article  PubMed  CAS  Google Scholar 

  62. Owa T, Yoshino H, Yoshimatsu K, Nagasu T. Cell cycle regulation in the G1 phase: a promising target for the development of new chemotherapeutic anticancer agents. Curr Med Chem 2001;8:1487–1503.

    Article  PubMed  CAS  Google Scholar 

  63. Zhou P, Jiang W, Zhang Y, et al. Antisense to cyclin D1 inhibits growth and reverses the transformed phenotype of human esophageal cancer cells. Oncogene 1995;11:571–580.

    PubMed  CAS  Google Scholar 

  64. Schrump DS, Chen A, Consoli U. Inhibition of lung cancer proliferation by antisense cyclin D. Cancer Gene Ther 1996:3:131–135.

    PubMed  CAS  Google Scholar 

  65. Arber N, Doki Y, Han EK-H, et al. Antisense to cyclin D1 inhibits the growth and tumorigenicity of human colon cancer cells. Cancer Res 1997;57:1569–1574.

    PubMed  CAS  Google Scholar 

  66. Sauter ER, Nesbit M, Litwin S, et al. Antisense cyclin D1 induces apoptosis and tumor shrinkage in human squamous carcinomas. Cancer Res 1999;59:4876–4881.

    PubMed  CAS  Google Scholar 

  67. Sauter ER, Yeo UC, Von Stemm A, et al. Cyclin D1 is a candidate oncogene in cutaneous melanoma. Cancer Res 2002;62:3200–3206.

    PubMed  CAS  Google Scholar 

  68. Schrump DS, Chen GA, Consuli U, et al. Inhibition of esophageal cancer proliferation by adenovirally mediated. delivery of p 16INK4. Cancer Gene Ther 1996; 3: 357–364.

    PubMed  CAS  Google Scholar 

  69. Jin X, Nguyen D, Zhamg WW, Roth JA. Cell cycle arrest and inhibition of tumor cell proliferation by the p 16INK gene mediated by an adenovirus vector. Cancer Res 1995;55:3250–3253.

    PubMed  CAS  Google Scholar 

  70. Sgambato A, Zhang Y- J, Ciaparrone M, et al. Overexpression of p27kiP1 inhibits the growth of both normal and transformed human mammary epithelial cells. Cancer Res 1998;58:3448–3454.

    PubMed  CAS  Google Scholar 

  71. Papadimitrakopoulou VA, Izzo J, Mao L, et al. Cyclin D 1 and p16 alterations in advanced premalignant lesions of the upper aerodigestive tract: role in response to chemoprevention and cancer development. Clin Cancer Res 2001;7:3127–3134.

    PubMed  CAS  Google Scholar 

  72. Dragnew KH, Freemantle SJ, Spinella MJ, Dmitrovsky E. Cyclin proteolysis as a retinoid cancer prevention mechanism. Ann NY Acad Sci 2001;952:13–22.

    Article  Google Scholar 

  73. Langenfeld J, Kiyokawa H, Sekula D, et al. Posttranslational regulation of cyclin D1 by retinoic acid: a chemopreventive mechanism. Proc Natl Acad Sci USA 1997;94:12070–12074.

    Article  PubMed  CAS  Google Scholar 

  74. Masuda M, Toh S, Koike K, et al. The roles of JNK1 and Stat3 in the response of head and neck cancer cell lines to combined treatment with all-trans-retinoic acid and 5-FU. Jpn J Cancer Res 2002;9:329–339.

    Article  Google Scholar 

  75. Lin JK, Liang YC, Lin-Shiau SY. Cancer chemoprevention by tea polyphenols through mitotic signal transduction blockade. Biochem Pharmacol 1999;58:911–915.

    Article  PubMed  CAS  Google Scholar 

  76. Ahmad N, Adhami VM, Gupta S, et al. Role of the retinoblastoma (pRb)-E2F/DP pathway in cancer chemopreventive effects of green tea polyphenol epigallocatechin-3-gallate. Arch Biochem Biophys 2002;398:125–131.

    Article  PubMed  CAS  Google Scholar 

  77. Masuda M, Suzui M, Weinstein IB. Effects of epigalloctechin-3-gallate (EGCG) on growth, EGFR signaling pathways, gene expression and chemosensitivity in human head and neck squamous cell carcinoma cell lines. Clin Cancer Res 2001;7:4220–4229.

    PubMed  CAS  Google Scholar 

  78. Casagrande F, Darbon JM. Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: regulation of cyclin-dependent kinases CDK2 and CDK 1. Biochem Pharmacol 2001;61:1205–1215.

    Article  PubMed  CAS  Google Scholar 

  79. Joe AK, Liu H, Suzui M, et al. Resveratrol induces growth inhibition, S-phase arrest, apoptosis, and changes in biomarker expression in several human cancer cell lines. Clin Cancer Res 2002;8:893–903.

    PubMed  CAS  Google Scholar 

  80. Ip C. Lessons from basic research in selenium and cancer prevention. J Nutr 1998;128:1845–1854.

    PubMed  CAS  Google Scholar 

  81. Ip C, Thompson HJ, Ganther HE. Selenium modulation of cell proliferation and cell cycle biomarkers in normal and premalignant cells of the rat mammary gland. Cancer Epidemiol Biomark Prey 2000;9:49–54.

    CAS  Google Scholar 

  82. Rao L, Puschner B, Prolla TA. Gene expression profiling of low selenium status in the mouse intestine: transcriptional activation of genes linked to DNA damage, cell cycle control and oxidative stress. J Nutr 2001;131:3175–3181.

    PubMed  CAS  Google Scholar 

  83. Liu M, Wikonkal NM, Brash DE. Induction of cyclindependent kinase inhibitors and G1 prolongation by the chemopreventive agent N-acetylcysteine. Carcinogenesis 1999;20:1869–1872.

    Article  PubMed  CAS  Google Scholar 

  84. Shirin H, Pinto JT, Kawabata Y, et al. W. Antiproliferative effects of S-allylmercaptocysteine on colon cancer cells, when tested alone or in combination with sulindac sulfide. Cancer Res 2001;61:725–731.

    PubMed  CAS  Google Scholar 

  85. Xiao D, Pinto JT, Soh JW, et al. Induction of apoptosis by the garlic-derived compound S-allylmercaptocysteine (SAMC) is associated with microtubule depolymerization and c-Jun NH(2)-terminal Kinase 1 activation. Cancer Res 2003;63:6825–6837.

    PubMed  CAS  Google Scholar 

  86. Soh J-W, Mao Y, Liu L, et al. Protein kinase G activates the JNK1 pathway via phosphorylation of MEKK1. J Biol Chem 2001;19:16,

    CAS  Google Scholar 

  87. Soh J-W, Mao Y, Liu L, et al. Protein kinase G activates the JNK1 pathway via phosphorylation of MEKK1. J Biol Chem 2001;19: 404–16,

    Google Scholar 

  88. Soh J-W, Mao Y, Liu L, et al. Protein kinase G activates the JNK1 pathway via phosphorylation of MEKK1. J Biol Chem 2001;19: 410.

    Google Scholar 

  89. Christov K, Ikui A, Shilkaitis A, et al. Cell proliferation, apoptosis and expression of cyclin D1 and cyclin E as potential biomarkers in tamoxifen treated mammary tumors. Breast Cancer Res 2003;77:253–264.

    Article  CAS  Google Scholar 

  90. Suzui M, Masuda M, Lim JTE, et al. Growth inhibition of human hepatoma cells by acylic retinoid is associated with inhibition of expression of cyclin D1. Cancer Res 2002;62:3997–4006.

    PubMed  CAS  Google Scholar 

  91. Carlson BA, Dunbay MM, Sausville EA, et al. Flavopiridol induces G1 arrest with inhibition of cyclin dependent kinase (CDK) 2 and CDK4 in human breast carcinoma cells. Cancer Res 1996;56:2973–2978.

    PubMed  CAS  Google Scholar 

  92. Carlson B, Lahusen T, Singh S, et al. Down-regulation of cyclin D1 by transcriptional repression in MCF-7 human breast carcinoma cells induced by flavopiridol. Cancer Res 1999;59:4634–4641.

    PubMed  CAS  Google Scholar 

  93. Schrump DS, Matthews W, Chen GA, et al. Flavopiridol mediates cell cycle arrest and apoptosis in esophageal cancer cells. Clin Cancer Res 1998;4:2885–2890.

    PubMed  CAS  Google Scholar 

  94. Akiyama T, Yoshida T, Tsujita T, et al. G1 phase accumulation induced by UCN-01 is associated with dephosphorylation of Rb and CDK2 proteins as well as induction of CDK inhibitor p21/Cipl/WAF1/Sdil in p53-mutated human epidermoid carcinoma A431 cells. Cancer Res 1997;57:1495–1501.

    PubMed  CAS  Google Scholar 

  95. Owa T, Yoshino H, Okauchi T, et al. Discovery of novel antitumor sulfonamides targeting G1 phase of the cell cycle. J Med Chem 1999;42:3789–3799.

    Article  PubMed  CAS  Google Scholar 

  96. De Azevedo WF, Leclerc S, Meijer L, et al. Inhibition of cyclin-dependent kinases by purine analogue: crystal structure of human cdk2 complexed with roscovitine. Eur J Biochem 1997;243:518–526.

    Article  PubMed  Google Scholar 

  97. Bramson H N, Corona J, Davis ST, et al. Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis. J Med Chem 2001;44:4339–4358.

    Article  PubMed  CAS  Google Scholar 

  98. Kent LL, Hull-Campbell NE, Lau T, et al. Characterization of novel inhibitors of cyclin-dependent kinases. Biochem Biophys Res Commun 1999;260:768–774.

    Article  PubMed  CAS  Google Scholar 

  99. Kubo A, Nakagawa K, Varma RK, et al. The p16 status of tumor cell lines identifies small molecule inhibitors specific for cyclin-dependent kinase 4. Clin Cancer Res 1999;5:4279–4286.

    PubMed  CAS  Google Scholar 

  100. Soni R, Muller L, Furet P, et al. Inhibition of cyclindependent kinase 4 (Cdk4) by fascaplysin, a marine natural product. Biochem Biophys Res Commun 2000;275:877–884.

    Article  PubMed  CAS  Google Scholar 

  101. Fry DW, Bedford DC, Harvey PH, et al. Cell cycle and biochemical effects of PD 0183812. A potent inhibitor of the cyclin D-dependent kinases CDK4 and CDK6. J Biol Chem 2001;276:16,

    Article  Google Scholar 

  102. Fry DW, Bedford DC, Harvey PH, et al. Cell cycle and biochemical effects of PD 0183812. A potent inhibitor of the cyclin D-dependent kinases CDK4 and CDK6. J Biol Chem 2001;276: 617–16

    Article  Google Scholar 

  103. Fry DW, Bedford DC, Harvey PH, et al. Cell cycle and biochemical effects of PD 0183812. A potent inhibitor of the cyclin D-dependent kinases CDK4 and CDK6. J Biol Chem 2001;276:623.

    Article  Google Scholar 

  104. Soni R, O’Reilly T, Furet P, et al. Selective in vivo and in vitro effects of a small molecule inhibitor of cyclindependent kinase 4. J Natl Cancer Inst 2001;93:436–446.

    Article  PubMed  CAS  Google Scholar 

  105. Sekulic A, Hudson CC, Homme JL, et al. A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells. Cancer Res 2000;60:3504–3513.

    PubMed  CAS  Google Scholar 

  106. Hashemolhosseini S, Nagamine Y, Morley SJ, et al. Rapamycin inhibition of the G1 to S transition is mediated by effects on cyclin D1 mRNA and protein stability. J Biol Chem 1998;273:14,

    Article  Google Scholar 

  107. Hashemolhosseini S, Nagamine Y, Morley SJ, et al. Rapamycin inhibition of the G1 to S transition is mediated by effects on cyclin D1 mRNA and protein stability. J Biol Chem 1998;273:424–14,

    Article  Google Scholar 

  108. Hashemolhosseini S, Nagamine Y, Morley SJ, et al. Rapamycin inhibition of the G1 to S transition is mediated by effects on cyclin D1 mRNA and protein stability. J Biol Chem 1998;273:14,424–14

    Article  Google Scholar 

  109. Kawamata S, Sakaida H, Hori T, et al. The upregulation of p27Kipl by rapamycin results in G1 arrest in exponentially growing T- cell lines. Blood 1998;91:561–569.

    PubMed  CAS  Google Scholar 

  110. Marks PA, Richon VM, Breslow R, Rifkind RA. Histone deacetylase inhibitors as new cancer drugs. Curr Opin Oncol 2001;13:477–483.

    Article  PubMed  CAS  Google Scholar 

  111. Galvez AF, Chen N, Macasieb J, de Lumen BO. Chemopreventive property of a soybean peptide (lunasin) that binds to deacetylated histones and inhibits acetylation. Cancer Res 2001;61:7473–7478.

    PubMed  CAS  Google Scholar 

  112. Saito A, Yamashita T, Mariko Y, et al. A synthetic inhibitor of histone deacetylase, MS-27–275, with marked in vivo antitumor activity against human tumors. Proc Natl Acad Sci USA 1999;96:4592–4597.

    Article  PubMed  CAS  Google Scholar 

  113. An WG, Hwang SG, Trepel JB, Blagosklonny MV. Protease inhibitor-induced apoptosis: accumulation of wt p53, p21 WAF 1 /CIP 1 and induction of apoptosis are independent markers of proteasome inhibition. Leukemia 2000;14:1276–1283.

    Article  PubMed  CAS  Google Scholar 

  114. Elliott PJ, Ross JS. The proteasome: a new target for novel drug therapies. Am J Clin Pathol 2001;116:637–646.

    Article  PubMed  CAS  Google Scholar 

  115. Otterson GA, Khleif SN, Chen W, et al. CDKN2 gene silencing in lung cancer by DNA hypermethylation nad kinetics of p 16INK4 protein induction by 5-aza-2’ deoxycytidine. Oncogene 1995;11:1211–1216.

    PubMed  CAS  Google Scholar 

  116. Biankin AV, Kench JG, Morey AL, et al. Overexpression of p21(WAF 1/CIP 1) is an early event in the development of pancreatic intraepithelial neoplasia. Cancer Res 2001;61:8830–8837.

    PubMed  CAS  Google Scholar 

  117. Tsujie M, Yamamoto H, Tomita N, et al. Expression of tumor suppressor gene p 16Ink4 products in primary gastric cancer. Oncology 2000;58:126–136.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Alessandro Sgambato MD, PhD
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  2. I. Bernard Weinstein MD
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Editors and Affiliations

  1. National Institutes of Health, Rockville, MD, USA

    Gary J. Kelloff MD  & Ernest T. Hawk MD, MPH  & 

  2. CCS Associates, Mountain View, CA, USA

    Caroline C. Sigman PhD

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Sgambato, A., Weinstein, I.B. (2004). Abnormalities in Cell Cycle Control in Human Cancer and Their Relevance to Chemoprevention. In: Kelloff, G.J., Hawk, E.T., Sigman, C.C. (eds) Cancer Chemoprevention. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-767-3_27

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  • DOI: https://doi.org/10.1007/978-1-59259-767-3_27

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-342-8

  • Online ISBN: 978-1-59259-767-3

  • eBook Packages: Springer Book Archive

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