Growth inhibition by anti‐estrogens and progestins in TGF‐β‐resistant and ‐sensitive breast‐tumor cells

Transforming growth factor β (TGF‐β) is a potent growth inhibitor of non‐malignant breast tissue, and TGF‐β resistance could play a role in tumorigenesis. Treatment of breast‐tumor cells with anti‐estrogens and progestins has been shown to correlate with an increase in the levels of secreted TGF‐β, suggesting that the growth inhibition observed with these (anti)hormones is mediated by this growth factor. In the present study we have investigated the effects of anti‐estrogens and progestins on breast‐tumor cell lines, which are either resistant or sensitive to TGF‐β. A hormone‐independent variant of the MCF7 cell line is shown to have lost its sensitivity to TGF‐β during its progression towards an autonomous phenotype, but has preserved its sensitivity to anti‐estrogens. In addition, evidence is presented showing that progestins and anti‐estrogens inhibit proliferation, irrespective of the sensitivity to TGF‐β in variants of the T47D cell line. Therefore, we conclude that, although TGF‐β seems an important growth inhibitor for mammary epithelial cells, both progestins and anti‐estrogens can inhibit cell proliferation independent of induced TGF‐β production. © 1996 Wiley‐Liss, Inc.