Growth factors as mediators of estrogen/antiestrogen action in human breast cancer cells.

Abstract

It is generally accepted that the induction and maintenance of breast cancer is, at some point and to a variable degree, under control by estrogen. However, the mechanisms by which estrogen regulates the proliferation of human breast cancer cells remain speculative. Recently it has been reported that breast cancer cells can synthesize and secrete a number of polypeptide growth factors or growth factor-like activities, including transforming growth factors alpha and beta (TGF—alpha and TGF—beta), the insulin-like growth factors I and II (IGF—I and IGF—II), platelet derived growth factor (PDGF), and the protease cathepsin D. For some of these growth factors, specific cell surface receptors have been identified in breast cancer cells. Furthermore, addition of exogenous growth factors to these cells under serum-free conditions induces growth stimulation (TGF-alpha, IGF-I, IGF-II, and cathepsin D) or growth inhibition (TGF—beta). Interestingly, the synthesis and secretion of these growth factors are regulated by estrogens and anti-estrogens in some estrogen receptor (ER)-positive hormone-dependent cells, whereas higher levels are expressed constitutively in some ER-negative hormone-independent cells. These data have led to the hypothesis that estrogens and antiestrogens regulate breast cancer progression and tumorigenicity indirectly by inducing the expression and secretion of polypeptide growth stimulators or inhibitors, which then bind and act on breast cancer cells in an autocrine fashion [1]. On the other hand, the growth advantage associated with hormone-independent breast cancer cells may be due to the high constitutive expression of autocrine growth factors.KeywordsBreast Cancer CellHuman Breast Cancer CellTransform Growth Factor AlphaEpidermal Growth Factor Receptor BlockadeType Beta Transform Growth FactorThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.