Ma. Krasilnikov et al., EFFECTS OF PROGESTERONE AND TAMOXIFEN ON EGF-DEPENDENT ACTIVATION OF PHOSPHOLIPID TURNOVER IN UTERINE AND MAMMARY ADENOCARCINOMA CELLS, Biochemistry, 58(6), 1993, pp. 671-676
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