EFFECTS OF PROGESTERONE AND TAMOXIFEN ON EGF-DEPENDENT ACTIVATION OF PHOSPHOLIPID TURNOVER IN UTERINE AND MAMMARY ADENOCARCINOMA CELLS

The in vitro effects of epidermal growth factor (EGF) and progesterone on phospholipid turnover in 19 human uterine adenocarcinomas (postsur gical material) has been studied In 58% of the tumors EGF increased P- 32 incorporation into basic cellular phospholipids, phosphatidylcholin e, and phosphoinositides. In EGF-insensitive cells progesterone did no t significantly change the basal level of phospholipid metabolism. In 10 of II tumors positively responsive to EGF, progesterone inhibited t he EGF-dependent activation of P-32 incorporation within 15 min after its addition to the cells. Analysis of the effects of EGF and antiestr ogen tamoxifen on phospholipid turnover in 22 human mammary tumors did not revealed any significant differences in the effect of tamoxifen o n tumor cells with different responsiveness to EGF. Independently of c ell responsiveness to EGF, tamoxifen slightly decreased P-32 incorpora tion into phosphatidylcholines and increased P-32 incorporation into p hosphoinositides. Addition of tamoxifen to cells previously stimulated by EGF or 17 beta-estradiol did not eliminate their effects on phosph olipid metabolism. Treatment of cells with the protein kinase C activa tor 12-O-tetradecanaylphorbol 13-acetate (TPA) completely blocked the effect of tamoxifen on phospholipid metabolism. Our data indicate that EGF-dependent activation of intracellular phospholipid turnover is un der the negative control of progesterone. The effect of tamoxifen in c ells is independent of EGF and probably is exerted through the inhibit ion of protein kinase C activity