Estrogen induction of growth factors specific for hormone-responsive mammary, pituitary, and kidney tumor cells.

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Abstract
The problem of estrogen-promoted tumor cell growth was studied extensively in an attempt to establish the direct mitogenic role of these steroid hormones. Cell lines from 3 estrogen-responsive tumors or cell populations: the H-301 kidney tumor cells established from a parent estrogen-dependent hamster kidney tumor, the GH3/C14 rat pituitary tumor cell line established as a subline of the original GH3 population and the MTW9/PL mammary cell line developed from a parent estrogen- and prolactin-responsive MT-W9A carcinogen-induced rat tumor. With all 3 cell lines, a paradox was encountered. Although estrogens are obligatory for tumor formation in vivo, no direct mitogenic effect of estrogens can be shown in culture when assayed by an increase in cell number. The possibility that estrogens may induce growth factors in vivo that are then responsible for tumor formation by the 3 cell lines described was considered. Experiments presented in this report show that extracts of rodent uterus, kidney or liver contain growth activity for these 3 tumor cell lines, estrogen treatment causes an increase in tissue content of these activities and the estrogen-induced activities are specific for the estrogen-responsive cells. These studies suggest that estrogen-responsive tumor growth in vivo includes the mechanism of estrogen .fwdarw. uterus, kidney or liver .fwdarw. specific growth factors .fwdarw. estrogen-responsive tumor cells.