Epidermal growth factor stimulates cell proliferation and inhibits functional differentiation of mouse mammary epithelial cells in culture.
Mouse mammary epithelial cells cultured on collagen gels multiplied and produced casein and alpha-lactalbumin in response to insulin, cortisol, and PRL. The addition of epidermal growth factor (EGF) at 50 ng/ml increased the total number of epithelial cells by 30-40% and thymidine incorporation into DNA 4.7-fold after 5 days of culture. In contrast, EGF inhibited hormonal induction of the synthesis of casein and alpha-lactalbumin in those cells by about 45% and 55%, respectively, without inhibiting total protein synthesis. Furthermore, EGF decreased casein mRNA activity by 55% and increased total mRNA activity by 66% in cells cultured with the three hormones. These effects of EGF were apparent at 0.1 ng/ml and were maximal at 50-100 ng/ml and could be reversed by its removal from the medium, followed by the addition of anti-EGF antibody. The inhibition of casein synthesis by EGF was unaffected by the concentrations of insulin, cortisol, and PRL. Other growth factors, such as fibroblast growth factor, multiplication-stimulating activity, nerve growth factor, and platelet-derived growth factor, did not simulate the effects of EGF. Cytarabine (1 microgram/ml), which inhibited thymidine incorporation into DNA by 94%, did not block the inhibitory action of EGF on casein synthesis. These results suggest that EGF serves as a regulator of hormone-dependent growth and differentiation of mammary epithelial cells.
D000818:Animals; D002364:Caseins / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D007768:Lactalbumin / Q000096:biosynthesis; D007774:Lactation; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism
D002364:Caseins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D004247:DNA; D007768:Lactalbumin