Effects of 12-O-tetradecanoylphorbol-13-acetate on the differentiation of simian virus 40-infected human keratinocytes.

We have studied the effects of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate on the differentiation of human epidermal keratinocytes infected by the oncogenic virus Simian Virus 40. The cells in monolayers exposed to a concentration of 12-O-tetradecanoylphorbol-13-acetate as low as 5 X 10(-10) M redistributed into dense patches within 48 hr. This morphological change was accompanied by a 10- to 30-fold increase in the production of cells cytochemically stained by orange G:acid fuchsin indicating keratinization and a 2- to 3-fold increase in the exfoliation of cornified envelope-bearing cells. The induced cellular differentiation occurred in parallel with an inhibition of cell growth. The biologically inactive congener 4 alpha-phorbol-12,13-didecanoate at equimolar concentrations did not affect the growth or differentiation of these cells. Binding studies using [3H]12-O-tetradecanoylphorbol-13-acetate revealed a binding site with characteristics similar to those found for other cell types (Kd = 17 nM; 1.25 X 10(5) available sites/cell).