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

The problem of estrogen-promoted tumor cell growth has been studied extensively in an attempt to establish the direct mitogenic role of these steroid hormones. We have developed cell lines from three 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 three of these cell lines, we have encountered a paradox: 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. We have thus considered the possibility that estrogens may induce growth factors in vivo that are then responsible for tumor formation by the three cell lines described. Experiments presented in this report show that extracts of rodent uterus, kidney, or liver contain growth activity for these three tumor cell lines, that estrogen treatment causes an increase in tissue content of these activities, and that 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 leads to uterus, kidney, or liver leads to specific growth factors leads to estrogen-responsive tumor cells.