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Title: A novel antiestrogenic mechanism in progesterone receptor-transfected breast cancer cells
Authors: Zheng, Z.-Y.
Bay, B.-H. 
Aw, S.-E.
Lin, V.C.-L.
Issue Date: 29-Apr-2005
Citation: Zheng, Z.-Y., Bay, B.-H., Aw, S.-E., Lin, V.C.-L. (2005-04-29). A novel antiestrogenic mechanism in progesterone receptor-transfected breast cancer cells. Journal of Biological Chemistry 280 (17) : 17480-17487. ScholarBank@NUS Repository.
Abstract: The expression of progesterone receptor (PR) is normally estrogen-dependent, and progesterone is only active in target cells following estrogen exposure. This study revealed that the effect of estrogen was markedly disrupted by estrogen-independent expression of PR. Transfection of PR in estrogen receptor (ER)-positive MCF-7 cells abolished the estradiol-17β growth stimulatory effect that was observed in the parental cells and the vector-transfected controls in a ligand-independent manner. The antiestrogenic effect was also observed at the level of gene transcription. Estradiol-17β (E2)-induced gene expression of pS2 and GREB1 was impaired by 50-75% after 24-72 h of E2 treatment in PR-transfected cells. Promoter interference assay revealed that PR transfection drastically inhibited E2-mediated ER binding to estrogen response elements (ERE). The antiestrogenic effects of transfected PR are associated with enhanced metabolism of E2. HPLC analysis of [3H]E2 in the samples indicated that the percentage of [3H]E2 metabolized by PR-transfected cells in 6 h is similar to that by vector-transfected control cells in 24 h (77 and 80%, respectively). The increased metabolism of E2 may, in turn, be caused by increased cellular uptake of E2, as demonstrated by whole cell binding of [3H]E2. The findings open up a new window for a hitherto unknown functional relationship between the PR and ER. The antiestrogenic effect of transfected PR also provides a potential therapeutic strategy for estrogen-dependent breast cancer. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.
Source Title: Journal of Biological Chemistry
ISSN: 00219258
DOI: 10.1074/jbc.M501261200
Appears in Collections:Staff Publications

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