Epidermal growth factor partially reverses the inhibitory effects of antiestrogens on T 47D human breast cancer cell growth.
When T 47D human breast cancer cells were treated with 10 nM of the potent antiestrogen, 4-hydroxyclomiphene, growth rate was reduced to about 50% of control. Simultaneous treatment with epidermal growth factor (EGF) and 4-hydroxyclomiphene led to a partial reversal of the growth inhibitory effect of the antiestrogen. The effect of EGF was concentration-dependent being half-maximal at 0.10 ng/ml (0.02 nM) and maximal at concentrations greater than 0.5 ng/ml (greater than 0.08 nM). Furthermore, EGF partially reversed the growth inhibitory effects of several other antiestrogens including tamoxifen, 4-hydroxytamoxifen, and LY 117018. These results are compatible with the hypothesis that part of the growth inhibitory effects of antiestrogens on breast cancer cell proliferation are mediated by inhibition of autocrine secretion of growth stimulatory peptides acting through the EGF receptor.
D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002996:Clomiphene / Q000031:analogs & derivatives / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D006801:Humans; D011759:Pyrrolidines / Q000494:pharmacology; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology
D004965:Estrogen Antagonists; D011759:Pyrrolidines; D013876:Thiophenes; D013629:Tamoxifen; C016601:afimoxifene; D002996:Clomiphene; D004815:Epidermal Growth Factor; C025430:LY 117018; C050622:4-hydroxyclomiphene