Contrasting ability of antiestrogens to inhibit MCF-7 growth stimulated by estradiol or epidermal growth factor

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Abstract

A potential mechanism is described by which a growth factor may prevent the action of antiestrogens or reactivate the growth of hormone-responsive breast carcinoma in patients undergoing tamoxifen (TAM) treatment. Epidermal growth factor (EGF)-stimulated growth (10−8M EGF) was assayed in the MCF-7 breast cancer cell line in the presence of various concentrations (10−10 to 10−6M) of three antiestrogens, 4-hydroxytamoxifen (OH TAM), TAM and ICI 164384. In each case, the EGF-stimulated increases in DNA were not inhibited by the antiestrogen. OH TAM and ICI 164384 inhibited estradiol (E2) stimulated cell proliferation in a dose-related fashion. However, in the presence of both E2 and EGF, these two antiestrogens inhibited E2 effects only; EGF promotion of growth was unaffected. Pretreatment of MCF-7 cells for 2 days with either OH TAM or ICI 164384 did not inhibit EGF-induced increases in cell proliferation. We propose that eventual antiestrogen therapeutic failure may be caused by the paracrine influences of growth factors from neighboring cells.

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  • Cited by (0)

    Supported by grants CA32713, CA14520 and funds awarded through University of Wisconsin, H. I. Romnes Faculty Fellowship and ICI plc (Pharmaceuticals Division) Macclesfield, U.K.

    A graduate student in the University of Wisconsin Cellular and Molecular Biology Program.

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