Effect of 12-O-tetradecanoylphorbol-13-acetate on intercellular communication in various clones of mouse epidermal JB6 cells.

Abstract

We studied gap junctional intercellular communication (IC) in various clones of mouse epidermal JB6 cells and the effect of the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA) on such communication. JB6 clones used included nonpromotable, promotable, and transformed clones, representing a spectrum in susceptibility to transformation from nontransformed, to initiated (postinitiated), to transformed cells. We used the dye transfer assay and the radioisotope transfer assay, and quantified IC both in homologous pairings, where IC among cells of a single clone was examined, and heterologous pairings, where cells of initiated or transformed clones were paired with cells of a nonpromotable clone. Both pairings showed good IC in the absence of TPA and poor IC in the presence of TPA. However, suppression of IC by TPA was more effective when cells had advanced in promotability. IC was more suppressed by TPA in heterologous pairing than in homologous pairing. These results implied that in advanced stages of promotion, the capability to retain IC with each other (homologous IC) and especially with their nontransformed counterpart (heterologous IC) is progressively lost. Thus we conclude that the interaction of initiated cells and transformed cells with nontransformed cells decreases progressively in this model system for tumor promotion and progression.