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Effect of diverse tumor promoters on the expression of gap‐junctional proteins connexin (Cx) 26, Cx31.1, and Cx43 in SENCAR mouse epidermis
Author(s) -
Budunova Irina V.,
Carbajal Steve,
Slaga Thomas J.
Publication year - 1996
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/(sici)1098-2744(199603)15:3<202::aid-mc6>3.0.co;2-j
Subject(s) - connexin , gap junction , biology , tumor promotion , promoter , epidermis (zoology) , microbiology and biotechnology , 12 o tetradecanoylphorbol 13 acetate , carcinogenesis , keratinocyte , gene expression , intracellular , gene , cell culture , biochemistry , phosphorylation , anatomy , genetics , phorbol ester , protein kinase c
The inhibition of gap‐junctional intercellular communication (GJIC) between initiated and surrounding normal cells by tumor promoters is believed to be important in the promotion stage of carcinogenesis. Therefore, we examined the effect of skin‐tumor promoters on the expression of the gap‐junctional proteins connexin (Cx) 26, Cx43, and Cx31.1 in SENCAR mouse skin. Animals were treated with 12‐ O ‐tetradecanoylphorbol‐13‐acetate (TPA) (8.3 nmol), okadaic acid (OA) (2.5 nmol), chrysarobin (220 nmol), or benzoyl peroxide (BzPo) (83 μmol). Northern blot and immunofluorescence analyses revealed that keratinocytes in adult mouse skin expressed Cx31.1 and Cx43 but not Cx26. All four of the skin‐tumor promoters switched on the Cx26 gene, transiently increased expression of Cx43, and significantly inhibited the expression of Cx31.1. The time courses for changes in Cx26, Cx31.1, and Cx43 mRNA levels coincided in most cases and in general corresponded well to the time‐response curves for hyperplastic changes in mouse skin. The peaks of Cx26 and Cx43 expression and Cx31.1 inhibition appeared 12 h after TPA application and 24 h after OA and chrysarobin application. BzPo elevated the levels of Cx26 and Cx43 transcripts later (peak at 2–4 d). In tumor promoter‐treated skin, Cx26 and Cx43 plaques were on the plasma membrane of most keratinocytes. Cx31.1 staining was much weaker than in untreated epidermis. Thus, tumor promoters induce a large change in the expression of several Cxs, which in turn may affect both the level of GJIC and the sensitivity of GJIC to regulatory factors. © 1996 Wiley‐Liss, Inc.