Growth regulatory peptide production by human breast carcinoma cells

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.