Recent reports suggest that many of the biological effects of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate are mediated via intracellular prostaglandin biosynthesis. We have investigated whether the induction of plasminogen activator by 12-O-tetradecanoylphorbol-13-acetate in cultured HeLa cells is similarly mediated. 12-O-Tetradecanoylphorbol-13-acetate (0.5 to 50 nM) increased intra- and extracellular plasminogen activators and stimulated E- and F-type prostaglandin production. Changes in prostaglandin biosynthesis preceded those in plasminogen activator by several hr. Indomethacin (0.5 microM) abolished prostaglandin production but had no effect on either the magnitude or the time course of induction of plasminogen activator. Similar results were obtained with human skin fibroblasts and MDCK cells. Prostaglandins E1, E2, F2 alpha, and I2 had no direct effect on plasminogen activator in HeLa cells or skin fibroblasts. We conclude that in these cells, phorbol ester independently induces plasminogen activator and prostaglandin biosynthesis.
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