c-Myc induction of programmed cell death may contribute to carcinogenesis: A perspective inspired by several concepts of chemical carcinogenesis

Cancer Biology and Therapy

Volumn 11, Issue 7, 2011, Pages 615-626

  Wang, Chenguang ^a   Tai, Yanhong ^b   Lisanti, Michael P ^a   Liao, D Joshua ^c  

^a THOMAS JEFFERSON UNIVERSITY   (United States)

^b CHINESE PLA GENERAL HOSPITAL   (China)

^c UNIVERSITY OF MINNESOTA   (United States)

Author keywords

Apoptosis; c Myc; Carcinogenesis; Compensatory proliferation; Cyclin D1

Indexed keywords

5 DIETHOXYCARBONYL 1,4 DIHYDROCOLLIDINE; CARCINOGEN; CHEMICAL AGENT; CYCLIN D1; DIHYDROPYRIDINE DERIVATIVE; H RAS PROTEIN; K RAS PROTEIN; MESSENGER RNA; MYC PROTEIN; ONCOPROTEIN; PROTEIN BCL 2; PROTEIN P53; RAS PROTEIN; SHORT HAIRPIN RNA; TRANSCRIPTION FACTOR E2F2; TRANSFORMING GROWTH FACTOR ALPHA; TUMOR SUPPRESSOR PROTEIN; UNCLASSIFIED DRUG;

APOPTOSIS; CANCER CELL; CELL CULTURE; CELL DEATH; CELL DIVISION; CELL KILLING; CELL MIGRATION; CELL PROLIFERATION; CELL SIZE; CELL SURVIVAL; CHEMICAL CARCINOGENESIS; CYTOTOXICITY; EPITHELIUM TUMOR; GENE ACTIVATION; GENE EXPRESSION; GENE OVEREXPRESSION; GROWTH INHIBITION; HUMAN; IN VITRO STUDY; IN VIVO STUDY; LIVER CARCINOGENESIS; LYMPHOMA; MITOSIS; NONHUMAN; ONCOGENE; ONCOGENE H RAS; ONCOGENE N RAS; PROTEIN INDUCTION; REVIEW; TRANSGENIC ANIMAL; TUMOR MICROENVIRONMENT; TUMOR SUPPRESSOR GENE; WILD TYPE;

ANIMALS; ANIMALS, GENETICALLY MODIFIED; APOPTOSIS; APOPTOSIS REGULATORY PROTEINS; CELL PROLIFERATION; CELL TRANSFORMATION, NEOPLASTIC; CYCLIN D; HUMANS; ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-MYC; TUMOR SUPPRESSOR PROTEIN P53;

EID: 79953325699     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.4161/cbt.11.7.14688     Document Type: Review

References (203)

1. Nesbit CE, Tersak JM, Prochownik EV. MYC oncogenes and human neoplastic disease. Oncogene 1999; 18:3004-16. (Pubitemid 29276540)
2. Graves JA, Rothermund K, Wang T, Qian W, Van HB, Prochownik EV. Point mutations in c-Myc uncouple neoplastic transformation from multiple other phenotypes in rat fibroblasts. PLoS One 2010; 5:13717.
3. Boxer LM, Dang CV. Translocations involving c-myc and c-myc function. Oncogene 2001; 20:5595-610. (Pubitemid 32928100)
4. Chung HJ, Levens D. c-myc expression: keep the noise down! Mol Cells 2005; 20:157-66.
5. 1/S escape. Cancer Biomark 2009; 5:41-9.
6. Cotter TG. Apoptosis and cancer: the genesis of a research field. Nat Rev Cancer 2009; 9:501-7.
7. Meyer N, Penn LZ. Reflecting on 25 years with MYC. Nat Rev Cancer 2008; 8:976-90.
8. Felsher DW. MYC inactivation elicits oncogene addiction through both tumor cell-intrinsic and host-dependent mechanisms. Genes Cancer 2010; 1:597-604.
9. Okuyama H, Endo H, Akashika T, Kato K, Inoue M. Downregulation of c-MYC protein levels contributes to cancer cell survival under dual deficiency of oxygen and glucose. Cancer Res 2010; 70:10213-23.
10. Sansom OJ, Meniel VS, Muncan V, Phesse TJ, Wilkins JA, Reed KR, et al. Myc deletion rescues Apc deficiency in the small intestine. Nature 2007; 446:676-9. (Pubitemid 46606884)
11. Wilkins JA, Sansom OJ. C-Myc is a critical mediator of the phenotypes of Apc loss in the intestine. Cancer Res 2008; 68:4963-6.
12. Athineos D, Sansom OJ. Myc heterozygosity attenuates the phenotypes of APC deficiency in the small intestine. Oncogene 2010; 29:2585-90.
13. Liao D, Thakur A, Wu J, Biliran H, Sarkar FH. Perspectives on c-Myc, cyclin d1 and their interaction in cancer formation, progression and response to chemotherapy. Crit Rev Oncog 2007; 13:93-158. (Pubitemid 350274298)
14. Liao JD, Adsay NV, Khannani F, Grignon D, Thakur A, Sarkar FH. Histological complexities of pancreatic lesions from transgenic mouse models are consistent with biological and morphological heterogeneity of human pancreatic cancer. Histol Histopathol 2007; 22:661-76. (Pubitemid 46647278)
15. Singh A, Sowjanya AP, Ramakrishna G. The wild-type Ras: road ahead. FASEB J 2005; 19:161-9. (Pubitemid 40189257)
16. Lin DI, Lessie MD, Gladden AB, Bassing CH, Wagner KU, Diehl JA. Disruption of cyclin D1 nuclear export and proteolysis accelerates mammary carcinogenesis. Oncogene 2008; 27:1231-42. (Pubitemid 351294688)
17. Wang TC, Cardiff RD, Zukerberg L, Lees E, Arnold A, Schmidt EV. Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature 1994; 369:669-71. (Pubitemid 24199473)
18. Deane NG, Parker MA, Aramandla R, Diehl L, Lee WJ, Washington MK, et al. Hepatocellular carcinoma results from chronic cyclin D1 overexpression in transgenic mice. Cancer Res 2001; 61:5389-95. (Pubitemid 32694916)
19. Guy CT, Webster MA, Schaller M, Parsons TJ, Cardiff RD, Muller WJ. Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc Natl Acad Sci USA 1992; 89:10578-82.
20. Siegel PM, Dankort DL, Hardy WR, Muller WJ. Novel activating mutations in the neu proto-oncogene involved in induction of mammary tumors. Mol Cell Biol 1994; 14:7068-77. (Pubitemid 24326370)
21. Siegel PM, Muller WJ. Mutations affecting conserved cysteine residues within the extracellular domain of Neu promote receptor dimerization and activation. Proc Natl Acad Sci USA 1996; 93:8878-83. (Pubitemid 26281985)
22. Siegel PM, Ryan ED, Cardiff RD, Muller WJ. Elevated expression of activated forms of Neu/ErbB-2 and ErbB-3 are involved in the induction of mammary tumors in transgenic mice: implications for human breast cancer. EMBO J 1999; 18:2149-64. (Pubitemid 29179172)
23. Herold S, Herkert B, Eilers M. Facilitating replication under stress: an oncogenic function of MYC? Nat Rev Cancer 2009; 9:441-4.
24. Prochownik EV. c-Myc: linking transformation and genomic instability. Curr Mol Med 2008; 8:446-58.
25. van RJ, Felsher DW. Myc and a Cdk2 senescence switch. Nat Cell Biol 2010; 12:7-9.
26. Campaner S, Doni M, Hydbring P, Verrecchia A, Bianchi L, Sardella D, et al. Cdk2 suppresses cellular senescence induced by the c-myc oncogene. Nat Cell Biol 2010; 12:54-9.
27. Grandori C, Robinson KL, Galloway DA, Swisshelm K. Functional link between Myc and the Werner gene in tumorigenesis. Cell Cycle 2004; 3:22-5. (Pubitemid 40268579)
28. Evan G, Littlewood T. A matter of life and cell death. Science 1998; 281:1317-22. (Pubitemid 28406818)
29. Evan GI, Vousden KH. Proliferation, cell cycle and apoptosis in cancer. Nature 2001; 411:342-8. (Pubitemid 32467043)
30. Ewen ME, Lamb J. The activities of cyclin D1 that drive tumorigenesis. Trends Mol Med 2004; 10:158-62. (Pubitemid 38410973)
31. Fiers W, Beyaert R, Declercq W, Vandenabeele P. More than one way to die: apoptosis, necrosis and reactive oxygen damage. Oncogene 1999; 18:7719-30. (Pubitemid 30052757)
32. Hoffman B, Liebermann DA. Apoptotic signaling by c-MYC. Oncogene 2008; 27:6462-72.
33. Tsuneoka M, Umata T, Kimura H, Koda Y, Nakajima M, Kosai K, et al. c-myc induces autophagy in rat 3Y1 fibroblast cells. Cell Struct Funct 2003; 28:195-204. (Pubitemid 37080958)
34. Dang CV. Antimalarial therapy prevents Myc-induced lymphoma. J Clin Invest 2008; 118:15-7.
35. Pelengaris S, Rudolph B, Littlewood T. Action of Myc in vivo - proliferation and apoptosis. Curr Opin Genet Dev 2000; 10:100-5. (Pubitemid 30113712)
36. Liao DJ, Dickson RB. Cell death in MMTV-c-myc transgenic mouse mammary tumors may not be typical apoptosis. Lab Invest 2003; 83:1437-49. (Pubitemid 37267827)
37. Liao DJ. The scavenger cell hypothesis of apoptosis: apoptosis redefined as a process by which a cell in living tissue is destroyed by phagocytosis. Med Hypotheses 2005; 65:23-8. (Pubitemid 40704523)
38. Lowe SW, Cepero E, Evan G. Intrinsic tumour suppression. Nature 2004; 432:307-15. (Pubitemid 39551658)
39. Han EK, Ng SC, Arber N, Begemann M, Weinstein IB. Roles of cyclin D1 and related genes in growth inhibition, senescence and apoptosis. Apoptosis 1999; 4:213-9. (Pubitemid 29378789)
40. Cagnol S, Chambard JC. ERK and cell death: mechanisms of ERK-induced cell death - apoptosis, autophagy and senescence. FEBS J 2010; 277:2-21.
41. Rounbehler RJ, Schneider-Broussard R, Conti CJ, Johnson DG. Myc lacks E2F1's ability to suppress skin carcinogenesis. Oncogene 2001; 20:5341-9. (Pubitemid 32844065)
42. Liao DJ, Natarajan G, Deming SL, Jamerson MH, Johnson M, Chepko G, Dickson RB. Cell cycle basis for the onset and progression of c-Myc-induced, TGFalpha-enhanced mouse mammary gland carcinogenesis. Oncogene 2000; 19:1307-17.
43. Sutherland KD, Vaillant F, Alexander WS, Wintermantel TM, Forrest NC, Holroyd SL, et al. c-myc as a mediator of accelerated apoptosis and involution in mammary glands lacking Socs3. EMBO J 2006; 25:5805-15. (Pubitemid 44967764)
44. Schulte-Hermann R, Bursch W, Kraupp-Grasl B, Oberhammer F, Wagner A. Programmed cell death and its protective role with particular reference to apoptosis. Toxicol Lett 1992; 64:569-74. (Pubitemid 23018799)
45. Schulte-Hermann R, Bursch W, Kraupp-Grasl B, Oberhammer F, Wagner A, Jirtle R. Cell proliferation and apoptosis in normal liver and preneoplastic foci. Environ Health Perspect 1993; 101:87-90. (Pubitemid 24096329)
46. Vaux DL, Cory S, Adams JM. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 1988; 335:440-2.
47. Marin MC, Hsu B, Stephens LC, Brisbay S, McDonnell TJ. The functional basis of c-myc and bcl-2 complementation during multistep lymphomagenesis in vivo. Exp Cell Res 1995; 217:240-7.
48. Strasser A, Harris AW, Bath ML, Cory S. Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2. Nature 1990; 348:331-3. (Pubitemid 120029100)
49. Smith DP, Bath ML, Metcalf D, Harris AW, Cory S. MYC levels govern hematopoietic tumor type and latency in transgenic mice. Blood 2006; 108:653-61. (Pubitemid 44061367)
50. Jager R, Herzer U, Schenkel J, Weiher H. Overexpression of Bcl-2 inhibits alveolar cell apoptosis during involution and accelerates c-myc-induced tumorigenesis of the mammary gland in transgenic mice. Oncogene 1997; 15:1787-95. (Pubitemid 27478621)
51. Jager R. Targeting the death machinery in mammary epithelial cells: Implications for breast cancer from transgenic and tissue culture experiments. Crit Rev Oncol Hematol 2007; 63:231-40. (Pubitemid 47126865)
52. Vaux DL. Early work on the function of Bcl-2, an interview with David Vaux. Cell Death Differ 2004; 11:28-32.
53. Wagner AJ, Small MB, Hay N. Myc-mediated apoptosis is blocked by ectopic expression of Bcl-2. Mol Cell Biol 1993; 13:2432-40. (Pubitemid 23097722)
54. Cory S, Vaux DL, Strasser A, Harris AW, Adams JM. Insights from Bcl-2 and Myc: malignancy involves abrogation of apoptosis as well as sustained proliferation. Cancer Res 1999; 59:1685-92.
55. Naud JF, Eilers M. PIM1 and MYC: a changing relationship? Nat Cell Biol 2007; 9:873-5.
56. Gerl R, Vaux DL. Apoptosis in the development and treatment of cancer. Carcinogenesis 2005; 26:263-70. (Pubitemid 40246548)
57. Pelengaris S, Khan M, Evan GI. Suppression of Myc-induced apoptosis in beta cells exposes multiple oncogenic properties of Myc and triggers carcinogenic progression. Cell 2002; 109:321-34. (Pubitemid 34606875)
58. Soucek L, Evan GI. The ups and downs of Myc biology. Curr Opin Genet Dev 2010; 20:91-5.
59. Pelengaris S, Khan M, Evan G. c-MYC: more than just a matter of life and death. Nat Rev Cancer 2002; 2:764-76. (Pubitemid 37328911)
60. Lowe SW, Lin AW. Apoptosis in cancer. Carcinogenesis 2000; 21:485-95. (Pubitemid 30137934)
61. Wodarz D, Komarova N. Can loss of apoptosis protect against cancer? Trends Genet 2007; 23:232-7.
62. Pettigrew CA, Cotter TG. Deregulation of cell death (apoptosis): implications for tumor development. Discov Med 2009; 8:61-3.
63. Jaattela M. Multiple cell death pathways as regulators of tumour initiation and progression. Oncogene 2004; 23:2746-56. (Pubitemid 38638838)
64. Tomlin JL, Guinn BA, Penn LZ, Berinstein NL. Bcl-2 and c-Myc co-operate in the Epstein-Barr virus-immortalized human B-cell line GM607 but do not confer tumorigenicity. Leuk Lymphoma 2005; 46:581-92. (Pubitemid 40584875)
65. de La CA, Mignon A, Fabre M, Gilbert E, Porteu A, Van DT, et al. Paradoxical inhibition of c-myc-induced carcinogenesis by Bcl-2 in transgenic mice. Cancer Res 1999; 59:5017-22. (Pubitemid 29472909)
66. Pierce RH, Vail ME, Ralph L, Campbell JS, Fausto N. Bcl-2 expression inhibits liver carcinogenesis and delays the development of proliferating foci. Am J Pathol 2002; 160:1555-60. (Pubitemid 34525634)
67. Vail ME, Pierce RH, Fausto N. Bcl-2 delays and alters hepatic carcinogenesis induced by transforming growth factoralpha. Cancer Res 2001; 61:594-601. (Pubitemid 32128620)
68. Murphy KL, Kittrell FS, Gay JP, Jager R, Medina D, Rosen JM. Bcl-2 expression delays mammary tumor development in dimethylbenz(a)anthracene-treated transgenic mice. Oncogene 1999; 18:6597-604.
69. 1 cyclin-dependent kinases. Oncogene 2002; 21:7765-75.
70. Vail ME, Chaisson ML, Thompson J, Fausto N. Bcl-2 expression delays hepatocyte cell cycle progression during liver regeneration. Oncogene 2002; 21:1548-55. (Pubitemid 34226142)
71. Joensuu H, Pylkkanen L, Toikkanen S. Bcl-2 protein expression and long-term survival in breast cancer. Am J Pathol 1994; 145:1191-8. (Pubitemid 24345666)
72. Gurova KV, Gudkov AV. Paradoxical role of apoptosis in tumor progression. J Cell Biochem 2003; 88:128-37. (Pubitemid 36015082)
73. Moreno E. Is cell competition relevant to cancer? Nat Rev Cancer 2008; 8:141-7.
74. Cavin LG, Wang F, Factor VM, Kaur S, Venkatraman M, Thorgeirsson SS, et al. Transforming growth factoralpha inhibits the intrinsic pathway of c-Myc-induced apoptosis through activation of nuclear factorkappaB in murine hepatocellular carcinomas. Mol Cancer Res 2005; 3:403-12. (Pubitemid 41045590)
75. Cheung RS, Brooling JT, Johnson MM, Riehle KJ, Campbell JS, Fausto N. Interactions between MYC and transforming growth factoralpha alter the growth and tumorigenicity of liver progenitor cells. Carcinogenesis 2007; 28:2624-31. (Pubitemid 350238966)
76. Factor VM, Kao CY, Santoni-Rugiu E, Woitach JT, Jensen MR, Thorgeirsson SS. Constitutive expression of mature transforming growth factor beta1 in the liver accelerates hepatocarcinogenesis in transgenic mice. Cancer Res 1997; 57:2089-95. (Pubitemid 27247017)
77. Kim H, Lee H, Yun Y. X-gene product of hepatitis B virus induces apoptosis in liver cells. J Biol Chem 1998; 273:381-5. (Pubitemid 28042221)
78. Terradillos O, Billet O, Renard CA, Levy R, Molina T, Briand P, et al. The hepatitis B virus X gene potentiates c-myc-induced liver oncogenesis in transgenic mice. Oncogene 1997; 14:395-404. (Pubitemid 27087102)
79. Cheung WC, Kim JS, Linden M, Peng L, Van NB, Polakiewicz RD, et al. Novel targeted deregulation of c-Myc cooperates with Bcl-X(L) to cause plasma cell neoplasms in mice. J Clin Invest 2004; 113:1763-73.
80. Lee HG, Chen Q, Wolfram JA, Richardson SL, Liner A, Siedlak SL, et al. Cell cycle re-entry and mitochondrial defects in myc-mediated hypertrophic cardiomyopathy and heart failure. PLoS One 2009; 4:7172.
81. Lee HG, Casadesus G, Nunomura A, Zhu X, Castellani RJ, Richardson SL, et al. The neuronal expression of MYC causes a neurodegenerative phenotype in a novel transgenic mouse. Am J Pathol 2009; 174:891-7.
82. Trudel M, Lanoix J, Barisoni L, Blouin MJ, Desforges M, L'Italien C, et al. C-myc-induced apoptosis in polycystic kidney disease is Bcl-2 and p53 independent. J Exp Med 1997; 186:1873-84. (Pubitemid 27524597)
83. Finch A, Prescott J, Shchors K, Hunt A, Soucek L, Dansen TB, et al. Bcl-xL gain of function and p19 ARF loss of function cooperate oncogenically with Myc in vivo by distinct mechanisms. Cancer Cell 2006; 10:113-20. (Pubitemid 44175905)
84. Radziszewska A, Schroer SA, Choi D, Tajmir P, Radulovich N, Ho JC, et al. Absence of caspase-3 protects pancreatic {beta}-cells from c-Myc-induced apoptosis without leading to tumor formation. J Biol Chem 2009; 284:10947-56.
85. Jamerson MH, Johnson MD, Korsmeyer SJ, Furth PA, Dickson RB. Bax regulates c-Myc-induced mammary tumour apoptosis but not proliferation in MMTV-c-myc transgenic mice. Br J Cancer 2004; 91:1372-9. (Pubitemid 39424800)
86. Hundley JE, Koester SK, Troyer DA, Hilsenbeck SG, Barrington RE, Windle JJ. Differential regulation of cell cycle characteristics and apoptosis in MMTV-myc and MMTV-ras mouse mammary tumors. Cancer Res 1997; 57:600-3. (Pubitemid 27085639)
87. Liao DJ, Dickson RB. c-Myc in breast cancer. Endocr Relat Cancer 2000; 7:143-64.
88. Verbeek S, van Lohuizen M, van der Valk, Domen J, Kraal G, Berns A. Mice bearing the E mu-myc and E mu-pim-1 transgenes develop pre-B-cell leukemia prenatally. Mol Cell Biol 1991; 11:1176-9. (Pubitemid 21895472)
89. Tuveson DA, Zhu L, Gopinathan A, Willis NA, Kachatrian L, Grochow R, et al. Mist1-KrasG12D knock-in mice develop mixed differentiation metastatic exocrine pancreatic carcinoma and hepatocellular carcinoma. Cancer Res 2006; 66:242-7. (Pubitemid 43166030)
90. Columbano A, Shinozuka H. Liver regeneration versus direct hyperplasia. FASEB J 1996; 10:1118-28. (Pubitemid 26276954)
91. Fan Y, Bergmann A. Apoptosis-induced compensatory proliferation. The Cell is dead. Long live the Cell! Trends Cell Biol 2008; 18:467-73.
92. Brockes JP, Kumar A. Comparative aspects of animal regeneration. Annu Rev Cell Dev Biol 2008; 24:525-49.
93. Bergmann A, Steller H. Apoptosis, stem cells and tissue regeneration. Sci Signal 2010; 3:8.
94. Laconi E, Doratiotto S, Vineis P. The microenvironments of multistage carcinogenesis. Semin Cancer Biol 2008; 18:322-9.
95. Farber E. Cell proliferation as a major risk factor for cancer: a concept of doubtful validity. Cancer Res 1995; 55:3759-62.
96. Solt DB, Farber E. A new principle for the analysis of chemical carcinogenesis. Nature 1976; 263:702-3.
97. Haddow A. Cellular inhibition and the origin of cancer. Acta Unio Int Contra Cancrum 1938; 3:342-53.
98. Laconi E, Pani P, Farber E. The resistance phenotype in the development and treatment of cancer. Lancet Oncol 2000; 1:235-41.
99. Laconi S, Pani P, Pillai S, Pasciu D, Sarma DS, Laconi E. A growth-constrained environment drives tumor progression in vivo. Proc Natl Acad Sci USA 2001; 98:7806-11. (Pubitemid 32642642)
100. Marongiu F, Doratiotto S, Montisci S, Pani P, Laconi E. Liver repopulation and carcinogenesis: two sides of the same coin? Am J Pathol 2008; 172:857-64.
101. Kohle C, Schwarz M, Bock KW. Promotion of hepatocarcinogenesis in humans and animal models. Arch Toxicol 2008; 82:623-31.
102. Farber E, Rubin H. Cellular adaptation in the origin and development of cancer. Cancer Res 1991; 51:2751-61.
103. Chang DW, Claassen GF, Hann SR, Cole MD. The c-Myc transactivation domain is a direct modulator of apoptotic versus proliferative signals. Mol Cell Biol 2000; 20:4309-19. (Pubitemid 30346625)
104. Dang CV, O'Donnell KA, Juopperi T. The great MYC escape in tumorigenesis. Cancer Cell 2005; 8:177-8. (Pubitemid 41317588)
105. Pusapati RV, Weaks RL, Rounbehler RJ, McArthur MJ, Johnson DG. E2F2 suppresses Myc-induced proliferation and tumorigenesis. Mol Carcinog 2009.
106. INK4b expression by Myc through association with Miz-1. Nat Cell Biol 2001; 3:392-9.
107. Coller HA, Grandori C, Tamayo P, Colbert T, Lander ES, Eisenman RN, et al. Expression analysis with oligonucleotide microarrays reveals that MYC regulates genes involved in growth, cell cycle, signaling and adhesion. Proc Natl Acad Sci USA 2000; 97:3260-5. (Pubitemid 30183289)
108. Bush A, Mateyak M, Dugan K, Obaya A, Adachi S, Sedivy J, et al. c-myc null cells misregulate cad and gadd45 but not other proposed c-Myc targets. Genes Dev 1998; 12:3797-802. (Pubitemid 29024841)
109. 2 arrest of normal fibroblasts. Proc Natl Acad Sci USA 2000; 97:10544-8.
110. Arvanitis C, Felsher DW. Conditional transgenic models define how MYC initiates and maintains tumorigenesis. Semin Cancer Biol 2006; 16:313-7. (Pubitemid 44311038)
111. Beer S, Zetterberg A, Ihrie RA, McTaggart RA, Yang Q, Bradon N, et al. Developmental context determines latency of MYC-induced tumorigenesis. PLoS Biol 2004; 2:332.
112. Beer S, Bellovin DI, Lee JS, Komatsubara K, Wang LS, Koh H, et al. Low-level shRNA cytotoxicity can contribute to MYC-induced hepatocellular carcinoma in adult mice. Mol Ther 2010; 18:161-70.
113. Beer S, Komatsubara K, Bellovin DI, Kurobe M, Sylvester K, Felsher DW. Hepatotoxin-induced changes in the adult murine liver promote MYC-induced tumorigenesis. PLoS One 2008; 3:2493.
114. Nikiforov MA, Riblett M, Tang WH, Gratchouck V, Zhuang D, Fernandez Y, et al. Tumor cell-selective regulation of NOXA by c-MYC in response to proteasome inhibition. Proc Natl Acad Sci USA 2007; 104:19488-93.
115. Thakur A, Sun Y, Bollig A, Wu J, Biliran H, Banerjee S, et al. Anti-invasive and antimetastatic activities of ribosomal protein S6 kinase 4 in breast cancer cells. Clin Cancer Res 2008; 14:4427-36.
116. Egle A, Harris AW, Bouillet P, Cory S. Bim is a suppressor of Myc-induced mouse B cell leukemia. Proc Natl Acad Sci USA 2004; 101:6164-9. (Pubitemid 38520545)
117. Hemann MT, Bric A, Teruya-Feldstein J, Herbst A, Nilsson JA, Cordon-Cardo C, et al. Evasion of the p53 tumour surveillance network by tumour-derived MYC mutants. Nature 2005; 436:807-11. (Pubitemid 41160633)
118. Hermeking H, Eick D. Mediation of c-Myc-induced apoptosis by p53. Science 1994; 265:2091-3.
119. Deb-Basu D, Aleem E, Kaldis P, Felsher DW. CDK2 is required by MYC to induce apoptosis. Cell Cycle 2006; 5:1342-7. (Pubitemid 43894291)
120. Yang H, Li TW, Ko KS, Xia M, Lu SC. Switch from Mnt-Max to Myc-Max induces p53 and cyclin D1 expression and apoptosis during cholestasis in mouse and human hepatocytes. Hepatology 2009; 49:860-70.
121. Opavsky R, Tsai SY, Guimond M, Arora A, Opavska J, Becknell B, et al. Specific tumor suppressor function for E2F2 in Myc-induced T cell lymphomagenesis. Proc Natl Acad Sci USA 2007; 104:15400-5. (Pubitemid 47502929)
122. Nass SJ, Li M, Amundadottir LT, Furth PA, Dickson RB. Role for Bcl-xL in the regulation of apoptosis by EGF and TGFbeta1 in c-myc overexpressing mammary epithelial cells. Biochem Biophys Res Commun 1996; 227:248-56. (Pubitemid 26370584)
123. Elson A, Deng C, Campos-Torres J, Donehower LA, Leder P. The MMTV/c-myc transgene and p53 null alleles collaborate to induce T-cell lymphomas, but not mammary carcinomas in transgenic mice. Oncogene 1995; 11:181-90.
124. McCormack SJ, Weaver Z, Deming S, Natarajan G, Torri J, Johnson MD, et al. Myc/p53 interactions in transgenic mouse mammary development, tumorigenesis and chromosomal instability. Oncogene 1998; 16:2755-66. (Pubitemid 28279341)
125. Liao DJ, Wang Y, Wu J, Adsay NV, Grignon D, Khanani F, et al. Characterization of pancreatic lesions from MT-tgfalpha, Ela-myc and MT-tgfalpha/Ela-myc single and double transgenic mice. J Carcinog 2006; 5:1-19.
126. Hong S, Pusapati RV, Powers JT, Johnson DG. Oncogenes and the DNA damage response: Myc and E2F1 engage the ATM signaling pathway to activate p53 and induce apoptosis. Cell Cycle 2006; 5:801-3. (Pubitemid 44145570)
127. Blyth K, Vaillant F, Hanlon L, Mackay N, Bell M, Jenkins A, et al. Runx2 and MYC collaborate in lymphoma development by suppressing apoptotic and growth arrest pathways in vivo. Cancer Res 2006; 66:2195-201.
128. Eischen CM, Weber JD, Roussel MF, Sherr CJ, Cleveland JL. Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis. Genes Dev 1999; 13:2658-69. (Pubitemid 29508553)
129. Jansen-Durr P, Meichle A, Steiner P, Pagano M, Finke K, Botz J, et al. Differential modulation of cyclin gene expression by MYC. Proc Natl Acad Sci USA 1993; 90:3685-9. (Pubitemid 23111432)
130. Marhin WW, Hei YJ, Chen S, Jiang Z, Gallie BL, Phillips RA, et al. Loss of Rb and Myc activation co-operate to suppress cyclin D1 and contribute to transformation. Oncogene 1996; 12:43-52. (Pubitemid 26041239)
131. Philipp A, Schneider A, Vasrik I, Finke K, Xiong Y, Beach D, et al. Repression of cyclin D1: a novel function of MYC. Mol Cell Biol 1994; 14:4032-43. (Pubitemid 24160809)
132. Cowling VH. Enhanced mRNA cap methylation increases cyclin D1 expression and promotes cell transformation. Oncogene 2010; 29:930-6.
133. Huerta M, Munoz R, Tapia R, Soto-Reyes E, Ramirez L, Recillas-Targa F, et al. Cyclin D1 is transcriptionally downregulated by ZO-2 via an E box and the transcription factor c-Myc. Mol Biol Cell 2007; 18:4826-36. (Pubitemid 350246685)
134. Chien J, Narita K, Rattan R, Giri S, Shridhar R, Staub J, et al. A role for candidate tumor-suppressor gene TCEAL7 in the regulation of c-Myc activity, cyclin D1 levels and cellular transformation. Oncogene 2008; 27:7223-34.
135. Guo QM, Malek RL, Kim S, Chiao C, He M, Ruffy M, et al. Identification of c-myc responsive genes using rat cDNA microarray. Cancer Res 2000; 60:5922-8.
136. Mateyak MK, Obaya AJ, Sedivy JM. c-Myc regulates cyclin D-Cdk4 and -Cdk6 activity but affects cell cycle progression at multiple independent points. Mol Cell Biol 1999; 19:4672-83. (Pubitemid 29289505)
137. Hermeking H, Rago C, Schuhmacher M, Li Q, Barrett JF, Obaya AJ, et al. Identification of CDK4 as a target of c-MYC. Proc Natl Acad Sci USA 2000; 97:2229-34. (Pubitemid 30134051)
138. Amendola D, De SM, Marchese R, Verga FC, Stigliano A, Carico E, et al. Myc downregulation affects cyclin D1/cdk4 activity and induces apoptosis via Smac/Diablo pathway in an astrocytoma cell line. Cell Prolif 2009; 42:94-109.
139. Biliran H Jr, Wang Y, Banerjee S, Xu H, Heng H, Thakur A, et al. Overexpression of cyclin D1 promotes tumor cell growth and confers resistance to cisplatin-mediated apoptosis in an elastase-myc transgene-expressing pancreatic tumor cell line. Clin Cancer Res 2005; 11:6075-86. (Pubitemid 41170340)
140. Biliran H Jr, Banerjee S, Thakur A, Sarkar FH, Bollig A, Ahmed F, et al. c-Myc-induced chemosensitization is mediated by suppression of cyclin D1 expression and nuclear factorkappa B activity in pancreatic cancer cells. Clin Cancer Res 2007; 13:2811-21. (Pubitemid 46788051)
141. Wu J, Wu SH, Bollig A, Thakur A, Liao DJ. Identification of the cyclin D1b mRNA variant in mouse. Mol Biol Rep 2009; 36:953-7.
142. Wang HL, Wang J, Xiao SY, Haydon R, Stoiber D, He TC, et al. Elevated protein expression of cyclin D1 and Fra-1 but decreased expression of c-Myc in human colorectal adenocarcinomas overexpressing beta-catenin. Int J Cancer 2002; 101:301-10. (Pubitemid 34983184)
143. Miliani de Marval PL, Macias E, Rounbehler R, Sicinski P, Kiyokawa H, Johnson DG, et al. Lack of cyclin-dependent kinase 4 inhibits c-myc tumorigenic activities in epithelial tissues. Mol Cell Biol 2004; 24:7538-47. (Pubitemid 39121481)
144. Li Z, Jiao X, Wang C, Shirley LA, Elsaleh H, Dahl O, et al. Alternative cyclin D1 splice forms differentially regulate the DNA damage response. Cancer Res 2010; 70:8802-11.
145. Suen TC, Hung MC. c-myc reverses neu-induced transformed morphology by transcriptional repression. Mol Cell Biol 1991; 11:354-62.
146. Barr LF, Campbell SE, Diette GB, Gabrielson EW, Kim S, Shim H, et al. c-Myc suppresses the tumorigenicity of lung cancer cells and downregulates vascular endothelial growth factor expression. Cancer Res 2000; 60:143-9. (Pubitemid 30058744)
147. Barsyte-Lovejoy D, Lau SK, Boutros PC, Khosravi F, Jurisica I, Andrulis IL, et al. The c-Myc oncogene directly induces the H19 noncoding RNA by allele-specific binding to potentiate tumorigenesis. Cancer Res 2006; 66:5330-7. (Pubitemid 43844958)
148. Keller U, Nilsson JA, Maclean KH, Old JB, Cleveland JL. NFκB 1 is dispensable for Myc-induced lymphomagenesis. Oncogene 2005; 24:6231-40.
149. Schlee M, Holzel M, Bernard S, Mailhammer R, Schuhmacher M, Reschke J, et al. C-myc activation impairs the NFkappaB and the interferon response: implications for the pathogenesis of Burkitt's lymphoma. Int J Cancer 2007; 120:1387-95. (Pubitemid 46355371)
150. Keller U, Huber J, Nilsson JA, Fallahi M, Hall MA, Peschel C, et al. Myc suppression of Nfkb2 accelerates lymphomagenesis. BMC Cancer 2010; 10:348.
151. Klapproth K, Sander S, Marinkovic D, Baumann B, Wirth T. The IKK2/NF-{kappa}B pathway suppresses MYC-induced lymphomagenesis. Blood 2009; 114:2448-58.
152. Eischen CM, Woo D, Roussel MF, Cleveland JL. Apoptosis triggered by Myc-induced suppression of Bcl-X(L) or Bcl-2 is bypassed during lymphomagenesis. Mol Cell Biol 2001; 21:5063-70.
153. Eischen CM, Packham G, Nip J, Fee BE, Hiebert SW, Zambetti GP, et al. Bcl-2 is an apoptotic target suppressed by both c-Myc and E2F-1. Oncogene 2001; 20:6983-93. (Pubitemid 33052191)
154. L. Mol Cell Biol 2003; 23:7256-70.
155. Tan A, Bitterman P, Sonenberg N, Peterson M, Polunovsky V. Inhibition of Myc-dependent apoptosis by eukaryotic translation initiation factor 4E requires cyclin D1. Oncogene 2000; 19:1437-47. (Pubitemid 30171175)
156. D'Cruz CM, Gunther EJ, Boxer RB, Hartman JL, Sintasath L, Moody SE, et al. c-MYC induces mammary tumorigenesis by means of a preferred pathway involving spontaneous Kras2 mutations. Nat Med 2001; 7:235-9.
157. Jang JW, Boxer RB, Chodosh LA. Isoform-specific ras activation and oncogene dependence during MYC- and Wnt-induced mammary tumorigenesis. Mol Cell Biol 2006; 26:8109-21. (Pubitemid 44631009)
158. Rapp UR, Korn C, Ceteci F, Karreman C, Luetkenhaus K, Serafin V, et al. MYC is a metastasis gene for non-small-cell lung cancer. PLoS One 2009; 4:6029.
159. Alexander WS, Bernard O, Cory S, Adams JM. Lymphomagenesis in Emu-myc transgenic mice can involve ras mutations. Oncogene 1989; 4:575-81. (Pubitemid 19139709)
160. Andrechek ER, Cardiff RD, Chang JT, Gatza ML, Acharya CR, Potti A, et al. Genetic heterogeneity of Myc-induced mammary tumors reflecting diverse phenotypes including metastatic potential. Proc Natl Acad Sci USA 2009; 106:16387-92.
161. Bodrug SE, Warner BJ, Bath ML, Lindeman GJ, Harris AW, Adams JM. Cyclin D1 transgene impedes lymphocyte maturation and collaborates in lymphomagenesis with the myc gene. EMBO J 1994; 13:2124-30. (Pubitemid 24139725)
162. Giuriato S, Ryeom S, Fan AC, Bachireddy P, Lynch RC, Rioth MJ, et al. Sustained regression of tumors upon MYC inactivation requires p53 or thrombospondin-1 to reverse the angiogenic switch. Proc Natl Acad Sci USA 2006; 103:16266-71. (Pubitemid 44715185)
163. Wu CH, van RJ, Yetil A, Fan AC, Bachireddy P, Felsher DW. Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation. Proc Natl Acad Sci USA 2007; 104:13028-33. (Pubitemid 351737587)
164. Gan L, Liu P, Lu H, Chen S, Yang J, McCarthy JB, et al. Cyclin D1 promotes anchorage-independent cell survival by inhibiting FOXO-mediated anoikis. Cell Death Differ 2009; 16:1408-17.
165. Roue G, Pichereau V, Lincet H, Colomer D, Sola B. Cyclin D1 mediates resistance to apoptosis through upregulation of molecular chaperones and consequent redistribution of cell death regulators. Oncogene 2008; 27:4909-20.
166. Noel EE, Yeste-Velasco M, Mao X, Perry J, Kudahetti SC, Li NF, et al. The association of CCND1 overexpression and cisplatin resistance in testicular germ cell tumors and other cancers. Am J Pathol 2010; 176:2607-15.
167. Shimura T, Kakuda S, Ochiai Y, Nakagawa H, Kuwahara Y, Takai Y, et al. Acquired radioresistance of human tumor cells by DNA-PK/AKT/GSK3beta-mediated cyclin D1 overexpression. Oncogene 2010; 29:4826-37.
168. Smalley KS, Lioni M, Dalla PM, Xiao M, Desai B, Egyhazi S, et al. Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E-mutated melanomas. Mol Cancer Ther 2008; 7:2876-83.
169. Kelly PN, Puthalakath H, Adams JM, Strasser A. Endogenous bcl-2 is not required for the development of Emu-myc-induced B-cell lymphoma. Blood 2007;
170. Yu Q, Geng Y, Sicinski P. Specific protection against breast cancers by cyclin D1 ablation. Nature 2001; 411:1017-21. (Pubitemid 32612319)
171. Freudenberg JA, Wang Q, Katsumata M, Drebin J, Nagatomo I, Greene MI. The role of HER2 in early breast cancer metastasis and the origins of resistance to HER2-targeted therapies. Exp Mol Pathol 2009; 87:1-11.
172. Freie BW, Eisenman RN. Ratcheting Myc. Cancer Cell 2008; 14:425-6.
173. Murphy DJ, Junttila MR, Pouyet L, Karnezis A, Shchors K, Bui DA, et al. Distinct thresholds govern Myc's biological output in vivo. Cancer Cell 2008; 14:447-57.
174. Shachaf CM, Gentles AJ, Elchuri S, Sahoo D, Soen Y, Sharpe O, et al. Genomic and proteomic analysis reveals a threshold level of MYC required for tumor maintenance. Cancer Res 2008; 68:5132-42.
175. Felsher DW. Tumor dormancy: death and resurrection of cancer as seen through transgenic mouse models. Cell Cycle 2006; 5:1808-11. (Pubitemid 44435323)
176. Felsher DW. Tumor dormancy and oncogene addiction. APMIS 2008; 116:629-37.
177. Weinstein IB, Joe A. Oncogene addiction. Cancer Res 2008; 68:3077-80.
178. Weinstein IB, Joe AK. Mechanisms of disease: Oncogene addiction - a rationale for molecular targeting in cancer therapy. Nat Clin Pract Oncol 2006; 3:448-57. (Pubitemid 44203817)
179. Weinstein IB. Cancer. Addiction to oncogenes - the Achilles heal of cancer. Science 2002; 297:63-4.
180. Montero L, Muller N, Gallant P. Induction of apoptosis by Drosophila Myc. Genesis 2008; 46:104-11. (Pubitemid 351498180)
181. de la Cova C, Abril M, Bellosta P, Gallant P, Johnston LA. Drosophila myc regulates organ size by inducing cell competition. Cell 2004; 117:107-16. (Pubitemid 38469902)
182. Donaldson TD, Duronio RJ. Cancer cell biology: Myc wins the competition. Curr Biol 2004; 14:425-7.
183. Gallant P. Myc, cell competition and compensatory proliferation. Cancer Res 2005; 65:6485-7. (Pubitemid 41060678)
184. Moreno E, Basler K. dMyc transforms cells into supercompetitors. Cell 2004; 117:117-29. (Pubitemid 38469903)
185. Gallant P. Drosophila Myc. Adv Cancer Res 2009; 103:111-44.
186. Siddall NA, Lin JI, Hime GR, Quinn LM. Myc - what we have learned from flies. Curr Drug Targets 2009; 10:590-601.
187. Bellosta P, Gallant P. Myc Function in Drosophila. Genes Cancer 2010; 1:542-6.
188. Gallant P, Steiger D. Myc's secret life without Max. Cell Cycle 2009; 8:3848-53.
189. Portela M, Casas-Tinto S, Rhiner C, Lopez-Gay JM, Dominguez O, Soldini D, et al. Drosophila SPARC is a self-protective signal expressed by loser cells during cell competition. Dev Cell 2010; 19:562-73.
190. Senoo-Matsuda N, Johnston LA. Soluble factors mediate competitive and cooperative interactions between cells expressing different levels of Drosophila Myc. Proc Natl Acad Sci USA 2007; 104:18543-8. (Pubitemid 350210733)
191. Benassayag C, Montero L, Colombie N, Gallant P, Cribbs D, Morello D. Human c-Myc isoforms differentially regulate cell growth and apoptosis in Drosophila melanogaster. Mol Cell Biol 2005; 25:9897-909. (Pubitemid 41572738)
192. Muncan V, Sansom OJ, Tertoolen L, Phesse TJ, Begthel H, Sancho E, et al. Rapid loss of intestinal crypts upon conditional deletion of the Wnt/Tcf-4 target gene c-Myc. Mol Cell Biol 2006; 26:8418-26. (Pubitemid 44748575)
193. Bettess MD, Dubois N, Murphy MJ, Dubey C, Roger C, Robine S, et al. c-Myc is required for the formation of intestinal crypts but dispensable for homeostasis of the adult intestinal epithelium. Mol Cell Biol 2005; 25:7868-78. (Pubitemid 41170145)
194. Li F, Xiang Y, Potter J, Dinavahi R, Dang CV, Lee LA. Conditional deletion of c-myc does not impair liver regeneration. Cancer Res 2006; 66:5608-12. (Pubitemid 43927111)
195. Levens D. You don't muck with MYC. Genes Cancer 2010; 1:547-54.
196. Baker NE, Li W. Cell competition and its possible relation to cancer. Cancer Res 2008; 68:5505-7.
197. Rhiner C, Moreno E. Super competition as a possible mechanism to pioneer precancerous fields. Carcinogenesis 2009; 30:723-8.
198. Hydbring P, Larsson LG. Tipping the balance: Cdk2 enables Myc to suppress senescence. Cancer Res 2010; 70:6687-91.
199. Hydbring P, Larsson LG. Cdk2: a key regulator of the senescence control function of Myc. Aging (Albany NY) 2010; 2:244-50.
200. Hydbring P, Bahram F, Su Y, Tronnersjo S, Hogstrand K, Von Der LN, et al. Phosphorylation by Cdk2 is required for Myc to repress Ras-induced senescence in cotransformation. Proc Natl Acad Sci USA 2010; 107:58-63.
201. Campaner S, Doni M, Verrecchia A, Faga G, Bianchi L, Amati B. Myc, Cdk2 and cellular senescence: Old players, new game. Cell Cycle 2010; 9:3655-61.
202. Macias E, Kim Y, Miliani de Marval PL, Klein-Szanto A, Rodriguez-Puebla ML. Cdk2 deficiency decreases ras/CDK4-dependent malignant progression, but not myc-induced tumorigenesis. Cancer Res 2007; 67:9713-20. (Pubitemid 47621218)
203. Liao DZ, Porsch-Hallstrom I, Gustafsson JA, Blanck A. Persistent sex differences in growth control of early rat liver lesions are programmed during promotion in the resistant hepatocyte model. Hepatology 1996; 23:835-9. (Pubitemid 26111999)