REGULATION OF PHOSPHOLIPID TURNOVER BY STEROID-HORMONES IN ENDOMETRIAL CARCINOMA AND BREAST-CANCER CELLS

To study the early effects of steroid hormones on cells we investigate d the influence of the sex steroids and tamoxifen on phospholipid turn over in endometrial carcinoma and breast cancer cells. Studies were pe rformed on 19 human uterine adenocarcinomas and 29 breast cancer tumor s. Progesterone in a final concentration of 10(-7) mol/l caused a twof old decrease of P-32 incorporation into phospholipids (phosphatidylcho line and phosphoinositides) in 85% of the uterine adenocarcinomas wher e the progesterone receptor (PR) content was more than 100 nmol/kg and only in 30% of the tumors where the PR content was less than 100 nmol /kg. Treatment of the cells with 10(-8) mol/l 17beta-estradiol or 10(- 8) mol/l epidermal growth factor led to an increase in P-32 incorporat ion into phospholipids. Analysis of the hormonal responsiveness of 29 human breast cancers showed that 17beta-estradiol increased P-32 incor poration into phospholipids in 47% of the tumors where the estradiol r eceptor (ER) content was more than 10 nmol/kg and in 21% of the recept or-negative tumors (ER < 10 nmol/kg) The results show that phospholipi d turnover in uterine and breast cells can be regulated by sex steroid s. Treatment of the breast cancer cells with the antiestrogen tamoxife n (10(-6) mol/l) led to an increase of P-32 incorporation into phospho inositides and a decrease of P-32 incorporation into phosphatidylcholi ne. Addition of an activator of protein kinase C, i.e. 2 x 10(-7) mol/ l 12-O-tetradecanoylphorbol-13-acetate, weakened the inhibitory effect of tamoxifen on phosphatidylcholine turnover. These findings suggest that tamoxifen action can be mediated via an alteration of the growth signal transducing system.