![]() We found that ER + mammary fibroblasts can mediate estrogen-induced proliferation in mammary epithelial cells via stroma-derived hepatocyte growth factor (HGF). To investigate the mechanism of the effects of estrogen-dependent stroma in the mammary gland, we have studied murine mammary epithelium in vitro using a minimally supplemented, serum-free, three-dimensional collagen-gel primary cell-culture system. Studies of mice from which the ERĪ± gene has been deleted indicate that the presence of ER + stroma is needed for an estrogen-induced proliferative response of the epithelium. Studies in both rodent and human mammary tissues have shown that markers of proliferation such as Ki 67, proliferating-cell nuclear antigen or BrdU incorporation and ERs are rarely colocalized in the same epithelial cells, suggesting that the proliferating epithelial cells are not the ER + cells. ![]() ![]() Estrogen receptors (ERs) are expressed in both epithelial and stromal cells, and certain estrogenic effects in the epithelium are modulated by mammary stroma both in vivo and in vitro (review ).
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