Growth inhibition by anti-estrogens and progestins in TGF-beta-resistant and -sensitive breast-tumor cells.
Transforming growth factor beta (TGF-beta) is a potent growth inhibitor of non-malignant breast tissue, and TGF-beta 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-beta, 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-beta. A hormone-independent variant of the MCF7 cell line is shown to have lost its sensitivity to TGF-beta 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-beta in variants of the T47D cell line. Therefore, we conclude that, although TGF-beta seems an important growth inhibitor for mammary epithelial cells, both progestins and anti-estrogens can inhibit cell proliferation independent of induced TGF-beta production.
Kalkhoven
E
E
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht.
Beraldi
E
E
Panno
M L
ML
De Winter
J P
JP
Thijssen
J H
JH
Van Der Burg
B
B
D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006131:Growth Inhibitors; D006801:Humans; D011372:Progestins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D011960:Receptors, Estrogen / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004965:Estrogen Antagonists; D006131:Growth Inhibitors; D011372:Progestins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D016212:Transforming Growth Factor beta