In cultures of basal epidermal cells obtained from ear skin of adult guinea pigs, the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate induces cellular proliferation which is prostaglandin dependent and inhibited by indomethacin. Inhibition by indomethacin can be overcome by prostaglandins E2 and F2α, with prostaglandin F2α being more effective. The concomitant induction of ornithine decarboxylase activity is insensitive to indomethacin inhibition. The nonpromoting derivative 4-O-methyl-12-O-tetradecanoylphorbol-13-acetate evokes a prostaglandin-independent, i.e., indomethacin-insensitive, stimulation of cell proliferation without inducing ornithine decarboxylase activity.
This work was supported by INSERM Grant CRL 802024 and by grants from the Deutsche Forschungsgemeinschaft.