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Estrogen and rapamycin effects on cell cycle progression in T47D breast cancer cells
Abstract:
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.
Insights
Estrogen drives breast cancer cell cycle progression, but pathways are unclear. Rapamycin inhibits this steroid-driven cell cycle, revealing new insights into hormone-dependent cancer therapies.
Area of Science:
- Endocrinology
- Cell Biology
- Cancer Research
Background:
- Estrogen and progesterone drive cell cycle progression in hormone-dependent breast cancer.
- Signal transduction pathways involved remain incompletely understood.
- Rapamycin, an immunosuppressant, inhibits cell cycle progression and aids pathway elucidation.
Purpose of the Study:
- To investigate the effects of rapamycin on cell cycle progression in estrogen-dependent breast cancer cells.
- To utilize a novel method for inducing S-phase to study these effects.
- To clarify the role of signal transduction pathways in estrogen-driven breast cancer.
Main Methods:
- Utilized T47D cells, a model for estrogen-dependent breast cancer.
- Employed estradiol-17-beta to induce S-phase without mitogen support.
- Assessed the effects of rapamycin on steroid-driven cell cycle transition from G1 to S-phase.
Main Results:
- Estradiol-17-beta alone induced S-phase in T47D cells at picomolar concentrations, independent of mitogens like insulin.
- Estrogen's S-phase induction was not highly specific, with estriol, estrone, and estradiol-17-beta-BSA showing similar efficacy.
- R5020, a progestin, also induced S-phase.
- Rapamycin effectively blocked the steroid-driven transition of cells from G1 to S-phase.
Conclusions:
- Estrogen can independently drive S-phase entry in hormone-dependent breast cancer cells.
- Rapamycin acts as a potent inhibitor of steroid-mediated cell cycle progression.
- These findings offer insights into targeting signal transduction pathways in breast cancer treatment.