An inducible mouse model for skin cancer reveals distinct roles for gain- and loss-of-function p53 mutations

Journal of Clinical Investigation

Volumn 117, Issue 7, 2007, Pages 1893-1901

  Caulin, Carlos ^a,b   Nguyen, Thao ^a   Lang, Gene A ^b   Goepfert, Thea M ^a   Brinkley, Bill R ^a   Cai, Wei Wen ^a   Lozano, Guillermina ^b   Roop, Dennis R ^a,c  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^c UCDHSC at Fitzsimons   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EOSIN; HEMATOXYLIN; KERATIN; PROTEIN P53;

ALLELE; ANEUPLOIDY; ANIMAL CELL; ANIMAL MODEL; ARTICLE; CARCINOGENESIS; CENTROSOME; CONTROLLED STUDY; GENE AMPLIFICATION; GENE EXPRESSION; GENE MUTATION; GENOTYPE; IMMUNOFLUORESCENCE; LYMPH NODE METASTASIS; MOUSE; NONHUMAN; PRIORITY JOURNAL; SKIN CARCINOGENESIS; SPINDLE CELL CARCINOMA;

ALLELES; ANEUPLOIDY; ANIMALS; ARGININE; CELL TRANSFORMATION, NEOPLASTIC; CENTROSOME; DISEASE MODELS, ANIMAL; ENZYME ACTIVATION; GENE EXPRESSION REGULATION, NEOPLASTIC; GLYCINE; LUNG NEOPLASMS; LYMPHATIC METASTASIS; MICE; MICE, INBRED C57BL; MUTATION; RAS PROTEINS; SKIN NEOPLASMS; TUMOR SUPPRESSOR PROTEIN P53;

EID: 34447130136     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI31721     Document Type: Article

References (54)

1. Alam, M., and Ratner, D. 2001. Cutaneous squamous-cell carcinoma. N. Engl. J. Med. 344:975-983.
2. Albert, M.R., and Weinstock, M.A. 2003. Keratinocyte carcinoma. CA Cancer J. Clin. 53:292-302.
3. Boukamp, P. 2005. Non-melanoma skin cancer: what drives tumor development and progression? Carcinogenesis. 26:1657-1667.
4. Pierceall, W.E., Goldberg, L.H., Tainsky, M.A., Mukhopadhyay, T., and Ananthaswamy, H.N. 1991. Ras gene mutation and amplification in human non-melanoma skin cancers. Mol. Carcinog. 4:196-202.
5. Spencer, J.M., Kahn, S.M., Jiang, W., DeLeo, V.A., and Weinstein, I.B. 1995. Activated ras genes occur in human actinic keratoses, premalignant precursors to squamous cell carcinomas. Arch. Dermatol. 131:796-800.
6. Balmain, A., and Brown, K. 1988. Oncogene activation in chemical carcinogenesis. Adv. Cancer Res. 51:147-182.
7. Ise, K., et al. 2000. Targeted deletion of the H-ras gene decreases tumor formation in mouse skin carcinogenesis. Oncogene. 19:2951-2956.
8. Rehman, I., 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.
9. Bailleul, B., et al. 1990. Skin hyperkeratosis and papilloma formation in transgenic mice expressing a ras oncogene from a suprabasal keratin promoter. Cell. 62:697-708.
10. Brown, K., Strathdee, D., Bryson, S., Lambie, W., and 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. 8:516-524.
11. Greenhalgh, D.A., et al. 1993. Induction of epidermal hyperplasia, hyperkeratosis, and papillomas in transgenic mice by a targeted v-Ha-ras oncogene. Mol. Carcinog. 7:99-110.
12. Vitale-Cross, L., Amornphimoltham, P., Fisher, G., Molinolo, A.A., and Gutkind, J.S. 2004. Conditional expression of K-ras in an epithelial compartment that includes the stem cells is sufficient to promote squamous cell carcinogenesis. Cancer Res. 64:8804-8807.
13. Bolshakov, S., et al. 2003. p53 mutations in human aggressive and nonaggressive basal and squamous cell carcinomas. Clin. Cancer Res. 9:228-234.
14. Brash, D.E., et al. 1991. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proc. Natl. Acad. Sci. U. S. A. 88:10124-10128.
15. Dittmer, D., et al. 1993. Gain of function mutations in p53. Nat. Genet. 4:42-46.
16. Sun, Y., Nakamura, K., Wendel, E., and Colburn, N. 1993. Progression toward tumor cell phenotype is enhanced by overexpression of a mutant p53 tumor-suppressor gene isolated from nasopharyngeal carcinoma. Proc. Natl. Acad. Sci. U. S. A. 90:2827-2831.
17. Cadwell, C., and Zambetti, G.P. 2001. The effects of wild-type p53 tumor suppressor activity and mutant p53 gain-of-function on cell growth. Gene. 277:15-30.
18. Lang, G.A., et al. 2004. Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome. Cell. 119:861-872.
19. Olive, K.P., et al. 2004. Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome. Cell. 119:847-860.
20. Wang, X.J., et al. 1998. Expression of a p53 mutant in the epidermis of transgenic mice accelerates chemical carcinogenesis. Oncogene. 17:35-45.
21. Caulin, C., et al. 2004. Inducible activation of oncogenic K-ras results in tumor formation in the oral cavity. Cancer Res. 64:5054-5058.
22. Jackson, E.L., et al. 2001. Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev. 15:3243-3248.
23. Roop, D.R., et al. 1989. Keratin expression in mouse epidermal tumors. Carcinog. Compr. Surv. 11:257-271.
24. Gimenez-Conti, I., et al. 1990. Early expression of type I K13 keratin in the progression of mouse skin papillomas. Carcinogenesis. 11:1995-1999.
25. Ko, L.J., and Prives, C. 1996. p53: puzzle and paradigm. Genes Dev. 10:1054-1072.
26. Jonkers, J., et al. 2001. Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer. Nat. Genet. 29:418-425.
27. Kemp, C.J., Donehower, L.A., Bradley, A., and Balmain, A. 1993. Reduction of p53 gene dosage does not increase initiation or promotion but enhances malignant progression of chemically induced skin tumors. Cell. 74:813-822.
28. de Vries, A., et al. 2002. Targeted point mutations of p53 lead to dominant-negative inhibition of wild-type p53 function. Proc. Natl. Acad. Sci. U. S. A. 99:2948-2953.
29. Klein-Szanto, A.J. 1989. Pathology of human and experimental skin tumors. Carcinog. Compr. Surv. 11:19-53.
30. Nischt, R., et al. 1988. Aberrant expression during two-stage mouse skin carcinogenesis of a type I 47-kDa keratin, K13, normally associated with terminal differentiation of internal stratified epithelia. Mol.Carcinog. 1:96-108.
31. Caulin, C., Bauluz, C., Gandarillas, A., Cano, A., and Quintanilla, M. 1993. Changes in keratin expression during malignant progression of transformed mouse epidermal keratinocytes. Exp. Cell Res. 204:11-21.
32. Han, G., et al. 2005. Distinct mechanisms of TGF-beta1-mediated epithelial-to-mesenchymal transition and metastasis during skin carcinogenesis. J. Clin. Invest. 115:1714-1723. doi:10.1172/JCI24399.
33. Murphy, K.L., Dennis, A.P., and Rosen, J.M. 2000. A gain of function p53 mutant promotes both genomic instability and cell survival in a novel p53-null mammary epithelial cell model. FASEB J. 14:2291-2302.
34. Brinkley, B.R. 2001. Managing the centrosome numbers game: from chaos to stability in cancer cell division. Trends Cell Biol. 11:18-21.
35. Goepfert, T.M., et al. 2002. Centrosome amplification and overexpression of aurora A are early events in rat mammary carcinogenesis. Cancer Res. 62:4115-4122.
36. Dlugosz, A., Merlino, G., and Yuspa, S.H. 2002. Progress in cutaneous cancer research. J. Investig. Dermatol. Symp. Proc. 7:17-26.
37. Tuveson, D.A., et al. 2004. Endogenous oncogenic K-ras(G12D) stimulates proliferation and widespread neoplastic and developmental defects. Cancer Cell. 5:375-387.
38. Chan, I.T., et al. 2004. Conditional expression of oncogenic K-ras from its endogenous promoter induces a myeloproliferative disease. J. Clin. Invest. 113:528-538. doi:10.1172/JCI200420476.
39. Mao, J.H., et al. 2004. Mutually exclusive mutations of the Pten and ras pathways in skin tumor progression. Genes Dev. 18:1800-1805.
40. Owens, D.M., Spalding, J.W., Tennant, R.W., and Smart, R.C. 1995. Genetic alterations cooperate with v-Ha-ras to accelerate multistage carcinogenesis in TG.AC transgenic mouse skin. Cancer Res. 55:3171-3178.
41. Quintanilla, M., Brown, K., Ramsden, M., and Balmain, A. 1986. Carcinogen-specific mutation and amplification of Ha-ras during mouse skin carcinogenesis. Nature. 322:78-80.
42. Nakazawa, H., et al. 1994. UV and skin cancer: specific p53 gene mutation in normal skin as a biologically relevant exposure measurement. Proc. Natl. Acad. Sci. U. S. A. 91:360-364.
43. Jonason, A.S., et al. 1996. Frequent clones of p53-mutated keratinocytes in normal human skin. Proc. Natl. Acad. Sci. U. S. A. 93:14025-14029.
44. Burns, P.A., et al. 1991. Loss of heterozygosity and mutational alterations of the p53 gene in skin tumours of interspecific hybrid mice. Oncogene. 6:2363-2369.
45. Ruggeri, B., et al. 1991. Alterations of the p53 tumor suppressor gene during mouse skin tumor progression. Cancer Res. 51:6615-6621.
46. Kelly-Spratt, K.S., Gurley, K.E., Yasui, Y., and Kemp, C.J. 2004. p19Arf suppresses growth, progression, and metastasis of Hras-driven carcinomas through p53-dependent and -independent pathways. PLoS Biol. 2:E242.
47. Soussi, T., and Lozano, G. 2005. p53 mutation heterogeneity in cancer. Biochem. Biophys. Res. Commun. 331:834-842.
48. Hingorani, S.R., et al. 2005. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell. 7:469-483.
49. Ziegler, A., et al. 1993. Mutation hotspots due to sunlight in the p53 gene of nonmelanoma skin cancers. Proc. Natl. Acad. Sci. U. S. A. 90:4216-4220.
50. Koster, M.I., Lu, S.L., White, L.D., Wang, X.J., and Roop, D.R. 2006. Reactivation of developmentally expressed p63 isoforms predisposes to tumor development and progression. Cancer Res. 66:3981-3986.
51. Flores, E.R., et al. 2005. Tumor predisposition in mice mutant for p63 and p73: evidence for broader tumor suppressor functions for the p53 family. Cancer Cell. 7:363-373.
52. Di Agostino, S., et al. 2006. Gain of function of mutant p53: the mutant p53/NF-Y protein complex reveals an aberrant transcriptional mechanism of cell cycle regulation. Cancer Cell. 10:191-202.
53. Roop, D.R., et al. 1984. Synthetic peptides corresponding to keratin subunits elicit highly specific antibodies. J. Biol. Chem. 259:8037-8040.
54. Mao, J.H., et al. 2005. Genomic instability in radiation-induced mouse lymphoma from p53 heterozygous mice. Oncogene. 24:7924-7934.