ESTROGEN ENHANCES EPIDERMAL GROWTH FACTOR-INDUCED DNA-SYNTHESIS IN MAMMARY EPITHELIAL-CELLS

Estradiol (E2) priming (1 nM for 48 h) of normal murine mammary gland epithelial cells significantly increased the response of those cells t o epidermal growth factor (EGF)-induced DNA synthesis. The synergism b etween E2 and EGF was evident in two aspects: After serum-free synchro nization for 24 h, more cells entered the S-phase of the cell cycle af ter E2 priming and when treated with 0.17 nM EGF (13%) than did contro l cells (1.3%) or cells treated with EGF (4%) or E2 (3.5%) alone; furt her, the dose of EGF required to elicit maximal response was reduced a n order of magnitude in estrogen-primed cells (0.17 nM) compared to co ntrols (1.7 mM). Estrogen alone, however, did not increase DNA synthes is in these cells. Ligand binding studies indicate that these effects of estrogen on proliferating mammary epithelial cells may be explained , at least in part, by a 3.7-fold increase in the number of high affin ity EGF-receptors observed in estrogen primed cells (7,300 receptors p er cell) compared to estrogen deprived cells (1,960 receptors/cell). ( C) 1993 Wiley-Liss, Inc.