Please use this identifier to cite or link to this item:
|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|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on May 23, 2018
WEB OF SCIENCETM
checked on May 8, 2018
checked on May 11, 2018
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.