Tumor promoters induce a transient expression of tumor-associated genes in both basal and differentiated cells of the mouse epidermis.

The effect of tumor promoters on the in vivo expression of tumor-associated, overexpressed genes was studied. Two of the tumor-associated genes, mal 1 and mal 2 were overexpressed already in the benign papilloma stage of mouse skin carcinogenesis. Overexpression of the other two genes, mal 4 and transin, was specific for the malignant state. Treatment of the normal adult epidermis with the complete tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and the incomplete, second-stage promoter 12-O-retinylphorbol-13-acetate (RPA) enhanced transiently the expression of the mal sequences and transin. Fractionation of the adult epidermis on Percoll gradients into basal cells and differentiated, suprabasal cells showed that expression of the mal sequences was enhanced by TPA in both basal and differentiated cells. In contrast, transin expression, which was undetectable in cells of the normal epidermis, was enhanced in only the basal cells of the TPA-treated epidermis. The non-tumor-promoting hyperplastic agent, ethylphenyl propiolate (EPP), applied to the skin at a hyperplastic dose level did not enhance the expression of the mal 4 or transin sequences in the epidermis and had only a slight enhancing effect on the levels of mal 1 and mal 2 transcripts in the epidermis. Our results suggest that the observed stimulated expression of mal 1 and mal 2 is related to proliferative processes, whereas stimulated expression of mal 4 and transin reflects tumor-promoter-specific responses.