Estrogen and rapamycin effects on cell cycle progression in T47D breast cancer cells.
The contribution of estrogen (and progesterone) in driving cell cycle progression of hormone dependent breast cancer cells is well documented, however, the roles of the various relevant signal transduction pathways remain unclear. The immunosuppressant rapamycin is a potent inhibitor of cell cycle progression and has been used to define signal transduction pathways. In this study we have determined rapamycin's effects on cell cycle progression in estrogen dependent breast cancer cells using a novel method of inducing S-phase. In this method estradiol-17-beta alone induced S-phase without mitogen support. In our studies the T47D cells were quite sensitive to estradiol-17-beta, with half-maximal induction in the picomolar range. indicating that the estrogen can induce S-phase in the absence of mitogens such as insulin. The estrogen response does not seem to be particularly specific because estriol estrone and estradiol-17-beta-BSA were about as effective as estradiol-17-beta. R5020, a progestin also induced S-Phase, while rapamycin blocked steroid driven transition of cells from G1 to S-phase.
Pang
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Department of Physiology, Medical College of Ohio, Toledo, OH 43614-5804, USA.
Faber
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D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D011397:Promegestone / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000187:drug effects; D016196:S Phase / Q000187:drug effects*; D020123:Sirolimus / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D011960:Receptors, Estrogen; D004958:Estradiol; D011397:Promegestone; D020123:Sirolimus