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.