EFFECT OF DIVERSE TUMOR PROMOTERS ON THE EXPRESSION OF GAP-JUNCTIONALPROTEINS CONNEXIN (CX)-26, CX31.1, AND CX43 IN SENCAR MOUSE EPIDERMIS

The inhibition of gap-junctional intercellular communication (GJIC) be tween initiated and surrounding normal cells by tumor promoters is bel ieved to be important in the promotion stage of carcinogenesis. Theref ore, we examined the effect of skin-tumor promoters on the expression of the gap-junctional proteins connexin (Cx) 26, Cx43, and Cx31.1 in S ENCAR 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 mu mol). Northern blot and immunofluorescence analyses revealed that keratinocytes in adult mous e skin expressed Cx31.1 and Cx43 but not Cx26. All four of the skin-tu mor promoters switched on the Cx26 gene, transiently increased express ion of Cx43, and significantly inhibited the expression of Cx31.1. The time courses for changes in Cx26, Cx31.1, and Cx43 mRNA levels coinci ded in most cases and in general corresponded well to the time-respons e curves for hyperplastic changes in mouse skin. The peaks of Cx26 and Cx43 expression and Cx31.1 inhibition appeared 12 h after TPA applica tion 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 pr omoter-treated skin, Cx26 and Cx43 plaques were on the plasma membrane of most keratinocytes. Cx31.1 staining was much weaker than in untrea ted epidermis. Thus, tumor promoters induce a large change in the expr ession of several Cxs, which in turn may affect both the level of GJIC and the sensitivity of GJIC to regulatory factors. (C) 1996 Wiley-Lis s, Inc.