PROLACTIN INHIBITS EPIDERMAL GROWTH-FACTOR (EGF)-STIMULATED SIGNALINGEVENTS IN MOUSE MAMMARY EPITHELIAL-CELLS BY ALTERING EGF RECEPTOR FUNCTION

We have previously shown that lactogenic hormones stimulate epidermal growth factor (EGF) mRNA accumulation in mouse mammary glands in vivo and in mouse mammary epithelial cells (NMuMG line). However, our in vi tro studies indicate that the lactogenic hormone prolactin (PRL) compl etely inhibits EGF-stimulated DNA synthesis. PRL does not alter choler a toxin or insulin-like growth factor-1-stimulated cell growth, thus t he inhibition appears to be specific for EGF. Our current studies are designed to evaluate the effects of PRL on EGF-stimulated signaling ev ents in the NMuMG cell line. Cells treated with PRL for 30 min demonst rated a loss of high affinity EGF-binding ability. After long-term PRL treatment (18 h) there was a decrease in EGF receptor (R) number, as determined by [I-125]EGF binding. PRL treatment (8 h) also decreased E GF-R mRNA levels. An EGF-stimulated increase in EGF-R mRNA observed 2- 4 h after treatment was decreased when PRL was added to the cultures. Furthermore, levels of EGF-stimulated tyrosine phosphorylation of the EGF-R (170 kDa) and phospholipase Cgamma (145 kDa) are dramatically de creased in cells treated with PRL. Also of great interest was a decrea se in EGF-stimulated c-myc mRNA in PRL-treated cells. We conclude that PRL is acting to down-regulate the EGF-R, thus limiting EGF-stimulate d cell signaling in mammary tissue.