INDUCTION OF PLASMINOGEN-ACTIVATOR AND PROSTAGLANDIN BIOSYNTHESIS IN HELA-CELLS BY 12-O-TETRADECANOYLPHORBOL-13-ACETATE

Abstract

Recent reports suggest that many of the biological effects of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate are mediated via intracellular prostaglandin biosynthesis. The effects of 12-O-tetradecanoylphorbol-13-acetate on plasminogen activation in cultured HeLa [human cervical carcinoma] cells were assessed in this study. 12-O-tetradecanoylphorbol-13-acetate (0.5-50 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 hours. Indomethacin (0.5 .mu.M) abolished prostaglandin production but had no effect on 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. In these cells, phorbol ester independently induces plasminogen activator and prostaglandin biosynthesis.