1932

Abstract

Over a century has elapsed since the first demonstration that exposure to chemicals in coal tar can cause cancer in animals. These observations provided an essential causal mechanistic link between environmental chemicals and increased risk of cancer in human populations. Mouse models of chemical carcinogenesis have since led to the concept of multistage tumor development through distinct stages of initiation, promotion, and progression and identified many of the genetic and biological events involved in these processes. Recent breakthroughs in DNA sequencing have now given us tools to dissect complete tumor genome architectures and revealed that chemically induced cancers in the mouse carry a high point mutation load and mutation signatures that reflect the causative agent used for tumor induction. Chemical carcinogenesis models may therefore provide a route to identify the causes of mutation signatures found in human cancers and further inform studies of therapeutic drug resistance and responses to immunotherapy, which are dependent on mutation load and genetic heterogeneity.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-cancerbio-050216-122002
2017-03-06
2024-06-24
Loading full text...

Full text loading...

/deliver/fulltext/cancerbio/1/1/annurev-cancerbio-050216-122002.html?itemId=/content/journals/10.1146/annurev-cancerbio-050216-122002&mimeType=html&fmt=ahah

Literature Cited

  1. Aleksic K, Lackner C, Geigl JB, Schwarz M, Auer M. et al. 2011. Evolution of genomic instability in diethylnitrosamine-induced hepatocarcinogenesis in mice. Hepatology 53:895–904 [Google Scholar]
  2. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SAJR, Behjati S. et al. 2013. Signatures of mutational processes in human cancer. Nature 500:415–21 [Google Scholar]
  3. Algarra I, Perez M, Serrano MJ, Garrido F, Gaforio JJ. 1998. c-K-ras overexpression is characteristic for metastases derived from a methylcholanthrene-induced fibrosarcoma. Invasion Metastasis 18:261–70 [Google Scholar]
  4. Aydinlik H, Ngugen TD, Moennikes O, Buchmann A, Schwarz M. 2001. Selective pressure during tumor promotion by phenobarbital leads to clonal outgrowth of β-catenin-mutated mouse liver tumors. Oncogene 20:7812–16 [Google Scholar]
  5. Balmain A, Pragnell I. 1983. Mouse skin carcinomas induced in vivo by chemical carcinogens have a transforming Harvey-ras oncogene. Nature 303:72–74 [Google Scholar]
  6. Balmain A, Yuspa SH. 2014. Milestones in skin carcinogenesis: the biology of multistage carcinogenesis. J. Investig. Dermatol. 134:e1E2–7 [Google Scholar]
  7. Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H. et al. 2009. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457:608–11 [Google Scholar]
  8. Berenblum I, Shubik P. 1947a. A new, quantitative, approach to the study of the stages of chemical carcinogenesis in the mouse's skin. Br. J. Cancer 1:383–91 [Google Scholar]
  9. Berenblum I, Shubik P. 1947b. The role of croton oil applications, associated with a single painting of a carcinogen, in tumour induction of the mouse's skin. Br. J. Cancer 1:379–82 [Google Scholar]
  10. Bigger CA, Sawicki JT, Blake DM, Raymond LG, Dipple A. 1983. Products of binding of 7,12-dimethylbenz(a)anthracene to DNA in mouse skin. Cancer Res 43:5647–51 [Google Scholar]
  11. Bizub D, Wood AW, Skalka AM. 1986. Mutagenesis of the Ha-ras oncogene in mouse skin tumors induced by polycyclic aromatic hydrocarbons. PNAS 83:6048–52 [Google Scholar]
  12. Borrello MG, Carbone G, Pierotti MA, Molla A, Della Porta G. 1988. Activated c-K-ras and c-N-ras oncogenes in 3-methylcholanthrene-induced BALB/c fibrosarcomas. Carcinogenesis 9:1517–19 [Google Scholar]
  13. Boutwell RK, Takigawa M, Verma AK, Ashendel CL. 1983. Observations on the mechanism of skin tumor promotion by phorbol esters. Princess Takamatsu Symp 14:177–93 [Google Scholar]
  14. Brown JR, Thornton JL. 1957. Percivall Pott (1714–1788) and chimney sweepers’ cancer of the scrotum. Br. J. Ind. Med. 14:68–70 [Google Scholar]
  15. Brown K, Buchmann A, Balmain A. 1990. Carcinogen-induced mutations in the mouse c-Ha-ras gene provide evidence of multiple pathways for tumor progression. PNAS 87:538–42 [Google Scholar]
  16. Brown K, Strathdee D, Bryson S, Lambie W, Balmain A. 1998. The malignant capacity of skin tumours induced by expression of a mutant H-ras transgene depends on the cell type targeted. Curr. Biol. 8:516–24 [Google Scholar]
  17. Buchmann A, Karcier Z, Schmid B, Strathmann J, Schwarz M. 2008. Differential selection for B-raf and Ha-ras mutated liver tumors in mice with high and low susceptibility to hepatocarcinogenesis. Mutat. Res 638:66–74 [Google Scholar]
  18. Castagna M, Takai Y, Kaibuchi K, Sano K, Kikkawa U, Nishizuka Y. 1982. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J. Biol. Chem. 257:7847–51 [Google Scholar]
  19. Chen B, You L, Wang Y, Stoner GD, You M. 1994. Allele-specific activation and expression of the K-ras gene in hybrid mouse lung tumors induced by chemical carcinogens. Carcinogenesis 15:2031–35 [Google Scholar]
  20. Clohessy JG, Pandolfi PP. 2015. Mouse hospital and co-clinical trial project—from bench to bedside. Nat. Rev. Clin. Oncol. 12:491–98 [Google Scholar]
  21. Da Costa RMG, Paula-Santos N, Rocha AF, Colaço A, Lopes C, Oliveira PA. 2014. The N-nitrosodiethylamine mouse model: sketching a timeline of evolution of chemically-induced hepatic lesions. Anticancer Res 7038:7029–38 [Google Scholar]
  22. Delclos KB, Nagle DS, Blumberg PM. 1980. Specific binding of phorbol ester tumor promoters to mouse skin. Cell 19:1025–32 [Google Scholar]
  23. Dias M, Cabrita S, Sousa E, Franca B, Patricio J, Oliveira C. 1999. Benign and malignant mammary tumors induced by DMBA in female Wistar rats. Eur. J. Gynaecol. Oncol. 20:285–88 [Google Scholar]
  24. Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. 2002. Cancer immunoediting: from immuno-surveillance to tumor escape. Nat. Immunol. 3:991–98 [Google Scholar]
  25. Engelman JA, Settleman J. 2008. Acquired resistance to tyrosine kinase inhibitors during cancer therapy. Curr. Opin. Genet. Dev. 18:73–79 [Google Scholar]
  26. Ewart-Toland A, Briassouli P, de Koning JP, Mao JH, Yuan J. et al. 2003. Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human. Nat. Genet. 34:403–12 [Google Scholar]
  27. Faustino-Rocha AI, Ferreira R, Oliveira PA, Gama A, Ginja M. 2015. N-methyl-N-nitrosourea as a mammary carcinogenic agent. Tumor Biol. 36:9095–117 [Google Scholar]
  28. Foley EJ. 1953. Antigenic properties of methylcholanthrene-induced tumors in mice of the strain of origin. Cancer Res 13:835–37 [Google Scholar]
  29. Forkert PG. 2010. Mechanisms of lung tumourigenesis by ethyl carbamate and vinyl carbamate. Drug Metab. Rev. 42:355–78 [Google Scholar]
  30. Friedewald WF, Rous P. 1994. The initiating and promoting elements in tumor production: an analysis of the effects of tar, benzpyrene, and methylcholanthrene on rabbit skin. J. Exp. Med. 80:101–26 [Google Scholar]
  31. Fujii H, Egami H, Chaney W, Pour P, Pelling J. 1990. Pancreatic ductal adenocarcinomas induced in Syrian hamsters by N-nitrosobis(2-oxopropyl)amine contain a c-Ki-ras oncogene with a point-mutated codon 12. Mol. Carcinog. 3:296–301 [Google Scholar]
  32. Gubin MM, Zhang X, Schuster H, Caron E, Ward JP. et al. 2014. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature 515:577–81 [Google Scholar]
  33. Hanahan D, Wagner EF, Palmiter RD. 2007. The origins of oncomice: a history of the first transgenic mice genetically engineered to develop cancer. Genes Dev 21:2258–70 [Google Scholar]
  34. He Z, Kosinska W, Zhao Z, Wu X, Guttenplan JB. 2012. Mutagenesis tissue-specific mutagenesis by N-butyl-N-(4-hydroxybutyl) nitrosamine as the basis for urothelial carcinogenesis. Mutat. Res. 742:92–95 [Google Scholar]
  35. Hecker E. 1968. Cocarcinogenic principles from the seed oil of Croton tiglium and from other Euphorbiaceae. Cancer Res 28:2338–49 [Google Scholar]
  36. Hoenerhoff MJ, Hong HH, Ton TV, Lanhousse SA, Sills RC. 2009. A review of the molecular mechanisms of chemically induced neoplasia in rat and mouse models in National Toxicology Program bioassays and their relevance to human cancer. Toxicol. Pathol. 37:835–48 [Google Scholar]
  37. Hsu IC, Metcalf RA, Sun T, Welsh JA, Wang NJ, Harris CC. 1991. Mutational hotspot in the p53 gene in human hepatocellular carcinomas. Nature 350:427–28 [Google Scholar]
  38. Ise K, Nakamura K, Nakao K, Shimizu S, Harada H. et al. 2000. Targeted deletion of the H-ras gene decreases tumor formation in mouse skin carcinogenesis. Oncogene 19:2951–56 [Google Scholar]
  39. Jacks T. 2005. Modeling cancer in the mouse. Harvey Lect 101:1–19 [Google Scholar]
  40. Jansen AP, Dreckschmidt NE, Verwiebe EG, Wheeler DL, Oberley TD, Verma AK. 2001. Relation of the induction of epidermal ornithine decarboxylase and hyperplasia to the different skin tumor-promotion susceptibilities of protein kinase Cα, -δ and -ε transgenic mice. Int. J. Cancer 93:635–43 [Google Scholar]
  41. Johnson BE, Mazor T, Hong C, Barnes M, Aihara K. et al. 2014. Mutational analysis reveals the origin and the therapy-driven evolution of recurrent glioma. Science 343:189–93 [Google Scholar]
  42. Keller RR, Gestl SA, Lu AQ, Hoke A, Feith DJ, Gunther EJ. 2016. Carcinogen-specific mutations in preferred Ras-Raf pathway oncogenes directed by strand bias. Carcinogenesis 37:810–16 [Google Scholar]
  43. Klein CA. 2009. Parallel progression of tumour and metastases. Nat. Rev. Cancer 9:302–12 [Google Scholar]
  44. Kucab JE, van Steeg H, Luijten M, Schmeiser HH, White PA. et al. 2015. TP53 mutations induced by BPDE in Xpa-WT and Xpa-Null human TP53 knock-in (Hupki) mouse embryo fibroblasts. Mutat. Res. 773:48–62 [Google Scholar]
  45. Kurowska M, Labocha-Pawlowska A, Gnizda D, Maluszynski M, Szarejko I. 2012. Molecular analysis of point mutations in a barley genome exposed to MNU and gamma rays. Mutat. Res. 738–739:52–70 [Google Scholar]
  46. Kwon MC, Berns A. 2013. Mouse models for lung cancer. Mol. Oncol. 7:165–77 [Google Scholar]
  47. Li S, Park H, Trempus CS, Gordon D, Liu Y. et al. 2013. A keratin 15 containing stem cell population from the hair follicle contributes to squamous papilloma development in the mouse. Mol. Carcinog. 52:751–59 [Google Scholar]
  48. Lindahl T. 2016. The intrinsic fragility of DNA (Nobel Lecture). Angew. Chem. Int. Ed. Engl. 55:8528–34 [Google Scholar]
  49. Loktionov A, Hollstein M, Martel N, Galendo D, Cabral JR. et al. 1990. Tissue-specific activating mutations of Ha- and Ki-ras oncogenes in skin, lung, and liver tumors induced in mice following transplacental exposure to DMBA. Mol. Carcinog. 3:134–40 [Google Scholar]
  50. Malkinson AM. 1991. Genetic studies on lung tumor susceptibility and histogenesis in mice. Environ. Health Perspect. 93:149–59 [Google Scholar]
  51. McCreery MQ, Halliwill KD, Chin D, Delrosario R, Hirst G. et al. 2015. Evolution of metastasis revealed by mutational landscapes of chemically induced skin cancers. Nat. Med. 21:1514–20 [Google Scholar]
  52. McFadden DG, Papagiannakopoulos T, Taylor-Weiner A, Stewart C, Carter SL. et al. 2014. Genetic and clonal dissection of murine small cell lung carcinoma progression by genome sequencing. Cell 156:1298–311 [Google Scholar]
  53. McFadden DG, Politic K, Bhutkara A, Chena FK, Song X. et al. 2016. Mutational landscape of EGFR-, MYC-, and Kras-driven genetically engineered mouse models of lung adenocarcinoma. PNAS 113:E6409–17 [Google Scholar]
  54. McGranahan N, Swanton C. 2015. Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. Cancer Cell 27:15–26 [Google Scholar]
  55. Medina D, Warner MR. 1976. Mammary tumorigenesis in chemical carcinogen-treated mice. IV. Induction of mammary ductal hyperplasias. J. Natl. Cancer Inst. 57:331–37 [Google Scholar]
  56. Megosh L, Halpern M, Farkash E, O'Brien TG. 1998. Analysis of ras gene mutational spectra in epidermal papillomas from K6/ODC transgenic mice. Mol. Carcinog. 22:145–49 [Google Scholar]
  57. Mitsui J, Nishikawa H, Muraoka D, Wang L, Noguchi T. et al. 2010. Two distinct mechanisms of augmented antitumor activity by modulation of immunostimulatory/inhibitory signals. Clin. Cancer Res. 16:2781–91 [Google Scholar]
  58. Mittal D, Gubin MM, Schreiber RD, Smyth MJ. 2014. New insights into cancer immunoediting and its three component phases—elimination, equilibrium and escape. Curr. Opin. Immunol. 27:16–25 [Google Scholar]
  59. Nagao M, Wakabayashi Y, Ushijima T, Toyota M, Totsuka Y, Sugimura T. 1996. Human exposure to carcinogenic heterocyclic amines and their mutational fingerprints in experimental animals. Environ. Health Perspect. 104:497–501 [Google Scholar]
  60. Nagase H, Mao J, Balmain A. 2003. Allele-specific Hras mutations and genetic alterations at tumor susceptibility loci in skin carcinomas from interspecific hybrid mice. Cancer Res 63:4849–53 [Google Scholar]
  61. Nakagama H, Nakanishi M, Ochiai M. 2005. Modeling human colon cancer in rodents using a food-borne carcinogen, PhIP. Cancer Sci 96:627–36 [Google Scholar]
  62. Nardella C, Lunardi A, Patnaik A, Cantley LC, Pandolfi PP. 2011. The APL paradigm and the “co-clinical trial” project. Cancer Discov 1:108–16 [Google Scholar]
  63. Nassar D, Latil M, Boeckx B, Lambrechts D, Blanpain C. 2015. Genomic landscape of carcinogen-induced and genetically induced mouse skin squamous cell carcinoma. Nat. Med. 21:946–54 [Google Scholar]
  64. Nebert DW, Dalton TP, Okey AB, Gonzalez FJ. 2004. Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer. J. Biol. Chem. 279:23847–50 [Google Scholar]
  65. Nik-Zainal S, Kucab JE, Morganella S, Glodzik D, Alexandrov LB. et al. 2015. The genome as a record of environmental exposure. Mutat. Res. 30:763–70 [Google Scholar]
  66. Nishikawa A, Imazawa T, Kuroiwa Y, Kitamura Y, Kanki K. et al. 2005. Induction of colon tumors in C57BL/6J mice fed MeIQx, IQ, or PhIP followed by dextran sulfate sodium treatment. Toxol. Sci. 84:243–48 [Google Scholar]
  67. Ogawa K, Uzvolgyi E, St. John MK, de Oliveira ML, Arnold L, Cohen SM. 1998. Frequent p53 mutations and occasional loss of chromosome 4 in invasive bladder carcinoma induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in B6D2F1 mice. Mol. Carcinog. 21:70–79 [Google Scholar]
  68. Ozturk M. 1991. p53 mutation in hepatocellular carcinoma after aflatoxin exposure. Lancet 338:1356–59 [Google Scholar]
  69. Parada LF, Tabin CJ, Shih C, Weinberg RA. 1982. Human EJ bladder carcinoma oncogene is homologue of Harvey sarcoma virus ras gene. Nature 297:474–78 [Google Scholar]
  70. Perucho M, Goldfarb M, Shimizu K, Lama C, Fogh J, Wigler M. 1981. Human-tumor-derived cell lines contain common and different transforming genes. Cell 27:467–76 [Google Scholar]
  71. Peterson SC, Eberl M, Vagnozzi AN, Belkadi A, Veniaminova NA. et al. 2015. Basal cell carcinoma preferentially arises from stem cells within hair follicle and mechanosensory niches. Cell Stem Cell 16:400–12 [Google Scholar]
  72. Petljak M, Alexandrov LB. 2016. Understanding mutagenesis through delineation of mutational signatures in human cancer. Carcinogenesis 37:531–40 [Google Scholar]
  73. Pfeifer GP, You Y-H, Besaratinia A. 2005. Mutations induced by ultraviolet light. Mutat. Res. 571:19–31 [Google Scholar]
  74. Pickering CR, Zhou JH, Lee JJ, Drummond JA, Peng SA. et al. 2014. Mutational landscape of aggressive cutaneous squamous cell carcinoma. Clin. Cancer Res. 20:6582–92 [Google Scholar]
  75. Polak P, Karlić R, Koren A, Thurman R, Sandstrom R. et al. 2015. Cell-of-origin chromatin organization shapes the mutational landscape of cancer. Nature 518:360–64 [Google Scholar]
  76. Poon SL, Pang ST, McPherson JR, Yu W, Huang KK. et al. 2013. Genome-wide mutational signatures of aristolochic acid and its application as a screening tool. Sci. Transl. Med. 5:197ra101 [Google Scholar]
  77. Popova NV, Suleimanian NE, Stepanova EA, Teti KA, Wu KQ, Morris RJ. 2004. Independent inheritance of genes regulating two subpopulations of mouse clonogenic keratinocyte stem cells. J. Investig. Dermatol. Symp. Proc. 9:253–60 [Google Scholar]
  78. Poulikakos PI, Zhang C, Bollag G, Shokat KM, Rosen N. 2010. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature 464:427–30 [Google Scholar]
  79. Pour PM, Salmasi SZ, Runge RG. 1978. Selective induction of pancreatic ductular tumors by single doses of N-nitrosobis(2-oxopropyl)amine in Syrian golden hamsters. Cancer Lett 4:317–23 [Google Scholar]
  80. Quigley DA, To MD, Perez-Losada J, Pelorosso FG, Mao JH. et al. 2009. Genetic architecture of mouse skin inflammation and tumour susceptibility. Nature 458:505–8 [Google Scholar]
  81. Quintanilla M, Brown K, Ramsden M, Balmain A. 1986. Carcinogen-specific mutation and amplification of Ha-ras during mouse skin carcinogenesis. Nature 322:78–80 [Google Scholar]
  82. Rehman I, Lowry DT, Adams C, Abdel-Fattah R, Holly A. et al. 2000. Frequent codon 12 Ki-ras mutations in mouse skin tumors initiated by N-methyl-N′-nitro-N-nitrosoguanidine and promoted by mezerein. Mol. Carcinog 27:298–307 [Google Scholar]
  83. Riggins RS, Pilcht Y. 1994. Immunity to spontaneous and methylcholanthrene-induced tumors in inbred mice. Cancer Res 24:1994–97 [Google Scholar]
  84. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V. et al. 2015. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348:124–29 [Google Scholar]
  85. Robert C, Arnault JP, Mateus C. 2011. RAF inhibition and induction of cutaneous squamous cell carcinoma. Curr. Opin. Oncol. 23:177–82 [Google Scholar]
  86. Santos E, Tronick SR, Aaronson SA, Pulciani S, Barbacid M. 1982. T24 human bladder carcinoma oncogene is an activated form of the normal human homologue of BALB- and Harvey-MSV transforming genes. Nature 298:343–47 [Google Scholar]
  87. Schmeiser HH, Janssen JW, Lyons J, Scherf HR, Pfau W. et al. 1990. Aristolochic acid activates ras genes in rat tumors at deoxyadenosine residues. Cancer Res 50:5464–69 [Google Scholar]
  88. Schulze K, Imbeaud S, Letouze E, Alexandrov LB, Calderaro J. et al. 2015. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets. Nat. Genet. 47:505–11 [Google Scholar]
  89. Shain AH, Yeh I, Kovalyshyn I, Sriharan A, Talevich E. et al. 2015. The genetic evolution of melanoma from precursor lesions. N. Engl. J. Med. 373:1926–36 [Google Scholar]
  90. Shih C, Shilo BZ, Goldfarb MP, Dannenberg A, Weinberg RA. 1979. Passage of phenotypes of chemically transformed cells via transfection of DNA and chromatin. PNAS 76:5714–18 [Google Scholar]
  91. Shilo BZ, Weinberg RA. 1981. Unique transforming gene in carcinogen-transformed mouse cells. Nature 289:607–9 [Google Scholar]
  92. Sikpi MO, Waters LC, Kraemer KH, Preston RJ, Mitra S. 1990. N-methyl-N-nitrosourea-induced mutations in a shuttle plasmid replicated in human cells. Mol. Carcinog. 3:30–36 [Google Scholar]
  93. Skopek TR, Walker VE, Cochrane JE, Craft TR, Cariello NF. 1992. Mutational spectrum at the Hprt locus in splenic T cells of B6C3F1 mice exposed to N-ethyl-N-nitrosourea. PNAS 89:7866–70 [Google Scholar]
  94. Song IY, Balmain A. 2015. Cellular reprogramming in skin cancer. Semin. Cancer Biol. 32:32–39 [Google Scholar]
  95. Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K. et al. 2011. The mutational landscape of head and neck squamous cell carcinoma. Science 333:1157–60 [Google Scholar]
  96. Su F, Viros A, Milagre C, Trunzer K, Bollag G. et al. 2012. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N. Engl. J. Med. 366:207–15 [Google Scholar]
  97. Sukumar S, Barbacid M. 1990. Specific patterns of oncogene activation in transplacentally induced tumors. PNAS 87:718–22 [Google Scholar]
  98. Szallasi Z, Krsmanovic L, Blumberg PM. 1993. Nonpromoting 12-deoxyphorbol 13-esters inhibit phorbol 12-myristate 13-acetate induced tumor promotion in CD-1 mouse skin. Cancer Res 53:2507–12 [Google Scholar]
  99. Takahashi M, Hori M, Mutoh M, Wakabayashi Y, Nakagama H. 2011. Experimental animal models of pancreatic carcinogenesis for prevention studies and their relevance to human disease. Cancers 3:582–602 [Google Scholar]
  100. Takigawa M, Verma AK, Simsiman RC, Boutwell RK. 1983. Inhibition of mouse skin tumor promotion and of promoter-stimulated epidermal polyamine biosynthesis by α-difluoromethylornithine. Carcinogenesis 43:3732–38 [Google Scholar]
  101. The Cancer Genome Atlas. 2012. Comprehensive genomic characterization of squamous cell lung cancers. Nature 489:519–25 [Google Scholar]
  102. To MD, Perez-Losada J, Mao J-H, Hsu J, Jacks T, Balmain A. 2006. A functional switch from lung cancer resistance to susceptibility at the Pas1 locus in Kras2LA2 mice. Nat. Genet 38:926–30 [Google Scholar]
  103. To MD, Quigley DA, Mao JH, Del Rosario R, Hsu J. et al. 2011. Progressive genomic instability in the FVB/KrasLA2 mouse model of lung cancer. Mol. Cancer Res. 9:1339–45 [Google Scholar]
  104. Turajlic S, Swanton C. 2016. Metastasis as an evolutionary process. Science 352:169–75 [Google Scholar]
  105. Ushmorov AG, Furstenberger G, Faissner A, Marks F. 1994. Effects of complete and incomplete tumor promoters on hair growth, angiogenesis, and tenascin expression in the skin of NMRI mice. Carcinogenesis 15:2739–45 [Google Scholar]
  106. Vasconcelos-Nobrega C, Colaco A, Lopes C, Oliveira PA. 2012. Review: BBN as an urothelial carcinogen. In Vivo 26:727–39 [Google Scholar]
  107. Verna L, Whysner J, Williams GM. 1996. N-nitrosodiethylamine mechanistic data and risk assessment: bioactivation, DNA-adduct formation, mutagenicity, and tumor initiation. Pharmacol. Ther. 71:57–81 [Google Scholar]
  108. Vesselinovitch SD, Mihailovich N. 1983. Kinetics of diethylnitrosamine hepatocarcinogenesis in the infant mouse. Cancer Res 43:4253–59 [Google Scholar]
  109. Viros A, Sanchez-Laorden B, Pedersen M, Furney SJ, Rae J. et al. 2014. Ultraviolet radiation accelerates BRAF-driven melanomagenesis by targeting TP53. Nature 511:478–82 [Google Scholar]
  110. Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr., Kinzler KW. 2013. Cancer genome landscapes. Science 339:1546–58 [Google Scholar]
  111. Wakabayashi Y, Mao J-H, Brown K, Girardi M, Balmain A. 2007. Promotion of Hras-induced squamous carcinomas by a polymorphic variant of the Patched gene in FVB mice. Nature 445:761–65 [Google Scholar]
  112. Wang GY, Wang J, Mancianti ML, Epstein EH. 2011. Basal cell carcinomas arise from hair follicle stem cells in Ptch1+/− mice. Cancer Cell 19:114–24 [Google Scholar]
  113. Wang MT, Holderfield M, Galeas J, Delrosario R, To MD. et al. 2015. K-Ras promotes tumorigenicity through suppression of non-canonical Wnt signaling. Cell 163:1237–51 [Google Scholar]
  114. Westcott PMK, Halliwill KD, To MD, Rashid M, Rust AG. et al. 2014. The mutational landscapes of genetic and chemical models of Kras-driven lung cancer. Nature 517:489–92 [Google Scholar]
  115. Wong CE, Yu JS, Quigley DA, To MD, Jen K-Y. et al. 2013. Inflammation and Hras signaling control epithelial–mesenchymal transition during skin tumor progression. Genes Dev 27:670–82 [Google Scholar]
  116. Yamagiwa K, Ichikawa K. 1918. Experimental study of the pathogenesis of carcinoma. J. Cancer Res. 27:123–81 [Google Scholar]
  117. You M, Candrian U, Maronpot RR, Stoner GD, Anderson MW. 1989. Activation of the Ki-ras protooncogene in spontaneously occurring and chemically induced lung tumors of the strain A mouse. PNAS 86:3070–74 [Google Scholar]
  118. Youssef KK, Van Keymeulen A, Lapouge G, Beck B, Michaux C. et al. 2010. Identification of the cell lineage at the origin of basal cell carcinoma. Nat. Cell Biol. 12:299–305 [Google Scholar]
  119. Yuspa SH. 1994. The pathogenesis of squamous cell cancer: lessons learned from studies of skin carcinogenesis—thirty-third G.H.A. Clowes Memorial Award Lecture. Cancer Res 54:1178–89 [Google Scholar]
  120. Zarbl H, Sukumar S, Arthur AV, Martin-Zanca D, Barbacid M. 1985. Direct mutagenesis of Ha-ras-1 oncogenes by N-nitroso-N-methylurea during initiation of mammary carcinogenesis in rats. Nature 315:382–85 [Google Scholar]
  121. Zayed S, Sorg B, Hecker E. 1984. Structure activity relations of polyfunctional diterpenes of the tigliane type, VI. Irritant and tumor promoting activities of semisynthetic mono and diesters of 12-deoxyphorbol. Planta Med 50:65–69 [Google Scholar]
/content/journals/10.1146/annurev-cancerbio-050216-122002
Loading
/content/journals/10.1146/annurev-cancerbio-050216-122002
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error