Anti-oestrogens induce the secretion of active transforming growth factor beta from human fetal fibroblasts.
The clinical use of anti-oestrogens in breast cancer therapy has traditionally been restricted to tumours that contain measurable oestrogen receptor protein. However, it is now widely recognised that the clinical response to adjuvant anti-oestrogen therapy appears to be independent of the oestrogen receptor content of the primary tumour. The study reported here was designed to investigate the possibility that human stromal cells can respond to anti-oestrogens by an increased synthesis of the inhibitory growth factor, transforming growth factor beta (TGF-beta). Two established human fetal fibroblast strains were used as models for the breast cancer stromal fibroblasts. These cells were found to respond to the addition of anti-oestrogens by a large increase in their synthesis of biologically active TGF-beta. Despite the application of ligand binding, immunoassay and Northern analysis, no oestrogen receptor or oestrogen receptor mRNA was detected in either of the human fetal fibroblasts strains. These observations may provide a mechanism of action of anti-oestrogens that is independent of the presence of oestrogen receptor in the tumour epithelial cells, and thus provide an explantation for the counter-intuitive results of adjuvant anti-oestrogen action.
Department of Surgery, Kings College School of Medicine and Dentistry, Rayne Institute, London, UK.
A A
AA
Colletta
L M
LM
Wakefield
F V
FV
Howell
K E
KE
van Roozendaal
D
D
Danielpour
S R
SR
Ebbs
M B
MB
Sporn
M
M
Baum
D015152:Blotting, Northern; D003907:Dexamethasone / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005333:Fetus; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008525:Medroxyprogesterone / Q000031:analogs & derivatives / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate; D009652:Norpregnenes / Q000494:pharmacology; D011397:Promegestone / Q000494:pharmacology; D012313:RNA / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D017312:Toremifene; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D004965:Estrogen Antagonists; D009652:Norpregnenes; D011960:Receptors, Estrogen; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D013196:Dihydrotestosterone; D013629:Tamoxifen; C033273:Gestodene; D004958:Estradiol; D012313:RNA; D017312:Toremifene; D003907:Dexamethasone; D011397:Promegestone; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone