Portal de Periódicos da CAPES

Increased expression of mutated Ha-ras during premalignant progression in SENCAR mouse skin

1999; Wiley; Volume: 26; Issue: 3 Linguagem: Inglês

10.1002/(sici)1098-2744(199911)26

1098-2744

Marcelo L. Rodríguez‐Puebla, Margaret LaCava, Marcela F. Bolontrade, Jamie L. Russell, Claudio J. Conti,

PI3K/AKT/mTOR signaling in cancer

Molecular CarcinogenesisVolume 26, Issue 3 p. 150-156 Brief Communication Increased expression of mutated Ha-ras during premalignant progression in SENCAR mouse skin Marcelo L. Rodriguez-Puebla, Marcelo L. Rodriguez-Puebla The University of Texas M. D. Anderson Cancer Center, Science Park–Research Division, Smithville, TXSearch for more papers by this authorMargaret LaCava, Margaret LaCava The University of Texas M. D. Anderson Cancer Center, Science Park–Research Division, Smithville, TXSearch for more papers by this authorMarcela F. Bolontrade, Marcela F. Bolontrade The University of Texas M. D. Anderson Cancer Center, Science Park–Research Division, Smithville, TXSearch for more papers by this authorJamie Russell, Jamie Russell The University of Texas M. D. Anderson Cancer Center, Science Park–Research Division, Smithville, TXSearch for more papers by this authorClaudio J. Conti, Corresponding Author Claudio J. Conti The University of Texas M. D. Anderson Cancer Center, Science Park–Research Division, Smithville, TXThe University of Texas M. D. Anderson Cancer Center, Science Park–Research Division, P.O. Box 389, Smithville, TX 78957.Search for more papers by this author Marcelo L. Rodriguez-Puebla, Marcelo L. Rodriguez-Puebla The University of Texas M. D. Anderson Cancer Center, Science Park–Research Division, Smithville, TXSearch for more papers by this authorMargaret LaCava, Margaret LaCava The University of Texas M. D. Anderson Cancer Center, Science Park–Research Division, Smithville, TXSearch for more papers by this authorMarcela F. Bolontrade, Marcela F. Bolontrade The University of Texas M. D. Anderson Cancer Center, Science Park–Research Division, Smithville, TXSearch for more papers by this authorJamie Russell, Jamie Russell The University of Texas M. D. Anderson Cancer Center, Science Park–Research Division, Smithville, TXSearch for more papers by this authorClaudio J. Conti, Corresponding Author Claudio J. Conti The University of Texas M. D. Anderson Cancer Center, Science Park–Research Division, Smithville, TXThe University of Texas M. D. Anderson Cancer Center, Science Park–Research Division, P.O. Box 389, Smithville, TX 78957.Search for more papers by this author First published: 22 October 1999 https://doi.org/10.1002/(SICI)1098-2744(199911)26:3 3.0.CO;2-PCitations: 19AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract The ras proto-oncogene family products are membrane-associated, guanine nucleotide–binding proteins that serve as a molecular switch for signal transduction pathways in a diverse array of organisms. In the mouse skin two-stage carcinogenesis model, a specific point mutation in Ha-ras codon 61 is responsible for the initiation event. Here we investigated whether Ha-ras protein and mRNA expression change during premalignant progression. Also, we assessed the Ha-ras mutated allele after these changes. To those ends, we analysed the Ha-ras expression profiles in normal and hyperplastic skin, papillomas, and squamous cell carcinomas by western blotting, reverse transcription–polymerase chain reaction, and in situ hybridization. Increased levels of Ha-ras expression were observed at specific times during promotion. These changes were followed by an increase in the level of expression of the Ha-ras mutated allele. These results suggest that increased expression of Ha-ras mutated alleles may have an important role during premalignant progression. Mol. Carcinog. 26:150–156, 1999. © 1999 Wiley-Liss, Inc. REFERENCES 1 Barbarcid M. Ras genes. Annual Rev Biochem 1987; 56: 779–828. Medline 2 Cahill MA. Signalling pathways: Jack of all cascades. Curr Biol 1996; 6: 16–19. Medline 3 Avruch J, Zhang X, Kyariakis J. Raf meets Ras: Completing the framework of a signal transduction pathway. Trends Biochem Sci 1994; 19: 279–283. Medline 4 Nakazawa H, Aguelon A, Yamasaki H. Identification and quantification of a carcinogen-induced molecular initiation event in cell transformation. Oncogene 1992; 7: 2295–2301. Medline 5 Slaga TJ. Cellular and molecular mechanisms involved in multistage skin carcinogenesis. In: CJ Conti, TJ Slaga, AJ Klein-Szanto, editors. Carcinogenesis, comprehensive survey, Vol. 11. New York: Raven Press; 1989. 1–18. 6 Balmain A, Pragnell I. Mouse skin carcinomas induced in vivo by chemical carcinogens have a transforming Harvey-ras oncogene. Nature 1983; 303: 72–74. Medline 7 Bizub D, Wood A, Skalka A. Mutagenesis of the Ha-ras oncogene in mouse skin tumors induced by polycyclic aromatic hydrocarbons. Proc Natl Acad Sci USA 1986; 83: 6048–6052. Medline 8 Roop D, Lowy D, Tambourin P, et al. An activated Harvey ras oncogene produces benign tumours on mouse epidermal tissue. Nature 1986; 323: 822–824. Medline 9 Quintanilla M, Brown K, Ramsden M, Balmain A. Carcinogen-specific mutation and amplification of Ha-ras during mouse skin carcinogenesis. Nature 1986; 322: 78–80. Medline 10 Aldaz CM, Conti CJ, Klein-Szanto AJP, Slaga T. Progressive dysplasia and aneuploidy are hallmarks of mouse skin papillomas: Relevance to malignancy. Proc Natl Acad Sci USA 1987; 84: 2029–2032. Medline 11 Aldaz MC, Trono D, Larcher F, Slaga T, Conti CJ. Sequential trisomization of chromosomes 6 and 7 in mouse skin premalignant lesions. Mol Carcinog 1989; 2: 22–26. Medline 12 Rodriguez-Puebla ML, LaCava M, Gimenez-Conti IB, Jonhson DG, Conti CJ. Deregulated expression of cell-cycle proteins during premalignant progression in SENCAR mouse skin. Oncogene 1998; 17: 2251–2258. Medline 13 Xu X, Lotan R. Nonisotopic in situ hybridization for the detection of nuclear retinoid receptor transcripts in tissue sections. Methods Mol Biol 1998; 89: 233–246. Medline 14 van Dierendonck JH, Wijsman JH, Keijzer R, van de Velde CJ, Cornelisse CJ. Cell-cycle-related staining patterns of anti-proliferating cell nuclear antigen monoclonal antibodies. Comparison with BrdUrd labeling and Ki-67 staining. Am J Pathol 1991; 138: 1165–1172. Medline 15 Fukuda M, Okamura K, Rohrbrach R, Bohm N, Fujita S. Changes in cell population kinetics during epidermal carcinogenesis. Cell and Tissue Kinetics 1978; 11: 611–621. Medline 16 Greenhalgh D, Rothnagel J, Quintanilla M, et al. Induction of epidermal hyperplasia, hyperkeratosis, and papillomas in transgenic mice by a targeted v-Ha-ras oncogene. Mol Carcinog 1993; 7: 99–110. Medline 17 Greenhalgh D, Quintanilla M, Orengo C, et al. Cooperation between v-fos and v-rasHA induces autonomous papillomas in transgenic epidermis but not malignant conversion. Cancer Res 1993; 53: 5071–5075. Medline 18 Leder A, Kuo A, Cardiff R, Sinn E, Leder P. v-Ha-ras transgene abrogates the initiation step in mouse skin tumorigenesis: Effects of phorbol esters and retinoic acid. Proc Natl Acad Sci USA 1990; 87: 9178–9182. Medline 19 Spalding J, Momma J, Elwell M, Tennant R. Chemically induced skin carcinogenesis in a transgenic mouse line [TG.AC] carrying a v-Ha-ras gene. Carcinogenesis 1993; 14: 1335–1341. Medline 20 Greenhalgh D, Welty D, Player A, Yuspa S. Two oncogenes, v-fos and v-ras, cooperate to convert normal keratinocytes to squamous cell carcinoma. Proc Natl Acad Sci USA 1990; 87: 643–647. Medline 21 Balmain A, Ramsden M, Bowden G, Smith J. Activation of the mouse cellular Harvey-ras gene in chemically induced benign skin papillomas. Nature 1984; 307: 658–660. Medline 22 Tofgard R, Roop D, Yuspa S. Proto-oncogene expression during two-stage carcinogenesis in mouse skin. Carcinogenesis 1985; 6: 655–657. Medline 23 Pelling J, Ernst S, Strawhecker J, Johnson J, Nairn R, Slaga T. Elevated expression of Ha-ras is an early event in two-stage skin carcinogenesis in SENCAR mice. Carcinogenesis 1986; 7: 1599–1602. Medline 24 Bianchi A, Aldaz MC, Conti CJ. Nonrandom duplication of the chromosome bearing a mutated Ha-ras-1 allele in mouse skin tumors. Proc Natl Acad Sci USA 1990; 87: 6902–6906. Medline 25 Bremner R, Balmain A. Genetic changes in skin tumor progression: Correlation between presence of a mutant ras gene and loss of heterozygosity on mouse chromosome 7. Cell 1990; 61: 407–417. Medline 26 Robles AI, Conti CJ. Early overexpression of cyclin D1 protein in mouse skin carcinogenesis. Carcinogenesis 1995; 16: 781–786. Medline 27 Bianchi AB, Fischer SM, Robles AI, Rinchik EM, Conti CJ. Overexpression of cyclin D1 in mouse skin carcinogenesis. Oncogene 1993; 8: 1127–1133. Medline 28 Filmus J, Robles AI, Shi W, Wong M, Colombo LL, Conti CJ. Induction of cyclin D1 overexpression by activated ras. Oncogene 1994; 9: 3627–3633. Medline 29 Winston JT, Coats SR, Wang Y-Z, Pledger WJ. Regulation of the cell cycle machinery by oncogenic ras. Oncogene 1996; 12: 127–134. Medline 30 Albanese C, Johnson J, Watanave G, et al. Transforming p21ras mutants and c-Ets-2 activate the cyclin D1 promoter through distinguishable regions. J Biol Chem 1995; 270: 23589–23597. Medline 31 Robles AI, Rodriguez-Puebla ML, Glick A, et al. Reduced skin tumor development in Cyclin D1 deficient mice highlights the oncogenic ras pathway in vivo. Genes Dev 1998; 12: 2469–2474. Medline 32 Rodriguez-Puebla ML, Robles AI, Conti CJ. Ras activity and cyclin D1 expression: An essential mechanism of mouse skin tumor development. Mol Carcinog 1999; 24: 1–6. Medline Citing Literature Volume26, Issue3November 1999Pages 150-156 ReferencesRelatedInformation