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01-07-2008 | Preclinical Study

Anti-estrogenic mechanism of unliganded progesterone receptor isoform B in breast cancer cells

Authors: Ze-Yi Zheng, Si-Min Zheng, Boon-Huat Bay, Swee-Eng Aw, Valerie C-L Lin

Published in: Breast Cancer Research and Treatment | Issue 1/2008

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.

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Title: Anti-estrogenic mechanism of unliganded progesterone receptor isoform B in breast cancer cells
Authors: Ze-Yi Zheng
Si-Min Zheng
Boon-Huat Bay
Swee-Eng Aw
Valerie C-L Lin
Publication date: 01-07-2008
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 1/2008
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-007-9711-8

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