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|Title:||Anti-estrogenic mechanism of unliganded progesterone receptor isoform B in breast cancer cells|
|Keywords:||Adenovirus-mediated gene delivery|
|Citation:||Zheng, Z.-Y., Zheng, S.-M., Bay, B.-H., Aw, S.-E., Lin, V.C.-L. (2008-07). Anti-estrogenic mechanism of unliganded progesterone receptor isoform B in breast cancer cells. Breast Cancer Research and Treatment 110 (1) : 111-125. ScholarBank@NUS Repository. https://doi.org/10.1007/s10549-007-9711-8|
|Abstract:||Over half of breast cancer cases are estrogen-dependent and strategies to combat estrogen-dependent breast cancer have been to either block the activation of estrogen receptor (ER) or diminish the supply of estrogens. Our previous work documented that estrogen-independent expression of progesterone receptor (PR) in MCF-7 cells markedly disrupted the effects of estrogen. In this study, we have developed an adenovirus-mediated gene delivery system to study the specific involvement of PR isoform A (PR-A) and PR-B in the anti-estrogenic effect and its mechanism of action. The results revealed that PR-B, but not PR-A, exhibited distinct anti-estrogenic effect on E2-induced cell growth, gene expression, and ER-ERE interaction in a ligand-independent manner. The anti-estrogenic effect of PR-B was also associated with heightened metabolism and increased cellular uptake of estradiol-17β (E2). We have also found that the B-upstream segment of PR-B alone was able to inhibit E2-induced ER-ERE interaction and cellular uptake of E2. Although PR-A alone did not affect E2-induced ER activity, it antagonized the anti-estrogenic effect of PR-B in a concentration-dependent manner. The findings suggest an important mechanism of maintaining a favorable level of ER activity by PR-A and PR-B in estrogen target cells for optimal growth and differentiation. The potential anti-estrogenic mechanism of PR-B may be exploited for breast cancer therapy. © 2007 Springer Science+Business Media, LLC.|
|Source Title:||Breast Cancer Research and Treatment|
|Appears in Collections:||Staff Publications|
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