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Induction of metallothionein mRNA by tumor promoters in mouse skin and its constitutive expression in papillomas
Author(s) -
Hashiba Hiroki,
Hosoi Junichi,
Karasawa Mika,
Yamada Shuhei,
Nose Kiyoshi,
Kuroki Toshio
Publication year - 1989
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940020208
Subject(s) - messenger rna , biology , metallothionein , tumor promotion , microbiology and biotechnology , gene expression , retinoic acid , northern blot , phorbol , tetradecanoylphorbol acetate , promoter , gene , biochemistry , enzyme , protein kinase c , carcinogenesis
A single topical application of 12‐ O ‐tetradecanoylphorbol‐13‐acetate (TPA) was found to induce mRNA of a metallothionein (MT) gene or genes in the skin of Sencar mice, and papillomas produced by repeated applications of TPA were shown to have elevated levels of MT mRNA. Induction of MT mRNA was maximal 4–8 h after application of TPA and returned to the control level 24 h later. A dose‐dependent increase of MT mRNA was observed with doses of TPA of 1–5 μg. Of the other promoters tested, phorbol‐12, 13‐didecanoate, mezerein, and the ionophore A23187 also induced MT mRNA, but 4‐ O ‐methyl‐TPA and benzoyl peroxide did not. Phorbol and 4α‐phorbol‐12, 13‐didecanoate, which are not promoters, also did not induce MT mRNA. Retinoic acid and 1α, 25‐dihydroxyvitamin D 3 , inhibitors of tumor promotion, did not induce MT mRNA themselves or inhibit the induction of MT mRNA by TPA. In C57BL/6 promotion‐resistant mice, TPA caused only slight induction of MT mRNA. These data suggest a correlation between induction of MT mRNA and epidermal hyperplasia. The constitutive elevation of MT mRNA levels in papillomas may be due to the loss, during the process of tumor promotion, of some mechanism regulating MT gene expression.