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).
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002472:Cell Transformation, Viral / Q000187:drug effects*; D002478:Cells, Cultured; D006801:Humans; D007231:Infant, Newborn; D007700:Kinetics; D008297:Male; D010704:Phorbols / Q000494:pharmacology*; D013539:Simian virus 40 / Q000235:genetics*; D012867:Skin / Q000187:drug effects; D012879:Skin Physiological Phenomena; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism / Q000494:pharmacology*
D010704:Phorbols; D013755:Tetradecanoylphorbol Acetate