Elevated expression of ha-ras is an early event in two-stage skin carcinogenesis in sencar mice

Jill C. Pelling, Sharon M. Ernst, Judith M. Strawhecker, Julie A. Johnson, Rodney S. Nairn, Thomas J. Slaga

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Abstract

Alterations in the expression of the Ha-ras oncogene were investigated in SENCAR mice epidermis at various stages of initiation and promotion during two-stage skin carcinogenesis in SENCAR mice. Adult SENCAR mice were treated with 200 nmol of the (+) enantiomer of benzo[a]pyrene 7, 8-diol 9, 10-epoxide-anti (BPDE-anti), a potent initiating agent, followed by repetitive treatments with the tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA). Other mice were 'sham'-initiated with the (-) enantiomer of BPDE-anti, which is inactive as a tumor initiator. Polyadenylated RNA was isolated from pre-tumor epidermis and tumors at eight different stages of tumorigenesis and analyzed for changes in Ha-ras expression using Northern blot hybridization. Significantly enhanced levels of Ha-ras RNA were observed in TPA-pro-moted papillomas as early as 7 weeks after initiation. Only trace amounts of Ha-ras RNA were present in untreated epidermis or epidermis treated with the (+) or (-) enantiomer followed by 2-12 treatments with TPA (pre-papilloma stage). Southern blot hybridization of tumor DNA indicated that the increased expression of the Ha-ras oncogene was not due to gene amplification. We conclude that elevated levels of Ha-ras expression can occur at an early stage of tumor development in mouse epidermis in vivo and may play a role in tumorigenesis.

Original languageEnglish (US)
Pages (from-to)1599-1602
Number of pages4
JournalCarcinogenesis
Volume7
Issue number9
DOIs
Publication statusPublished - Sep 1 1986

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ASJC Scopus subject areas

  • Cancer Research

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Pelling, J. C., Ernst, S. M., Strawhecker, J. M., Johnson, J. A., Nairn, R. S., & Slaga, T. J. (1986). Elevated expression of ha-ras is an early event in two-stage skin carcinogenesis in sencar mice. Carcinogenesis, 7(9), 1599-1602. https://doi.org/10.1093/carcin/7.9.1599