The mechanisms by which human breast cancers regulate their own growth have been studied by us in an in virto model system. We showed that specific growth factors (IGF-I, TGFα, PDGF) are secreted by human breast cancer cells. A variety of experiments suggest that they are involved in tumor growth and progession. These activities are induced by estradiol in hormone-dependent breast cancer cells and secreted constitutively by estrogen-independent cells. Concentrates of conditioned medium derived from breast cancer cells can induce the growth of hormone-dependent cells in vivo in athymic nude mice. Hormone-dependent breast cancer cells also secrete TGFβ. TGFβ is growth inhibitory. Growth inhibitors such as antiestrogens or glucocorticoids increase TGFβ secretion. An antiestrogen-resistant mutant of MCF-7 cells does not secrete TGFβ when treated with antiestrogen, but is growth inhibited when treated with exogenous TGFβ. Thus, TGFβ functions as a negative autocrine growth regulator and is probably responsible for some of the growth inhibitory effects of antiestrogens.
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