Please use this identifier to cite or link to this item:
|Title:||A novel antiestrogenic mechanism in progesterone receptor-transfected breast cancer cells|
|Source:||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. https://doi.org/10.1074/jbc.M501261200|
|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|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Feb 27, 2018
WEB OF SCIENCETM
checked on Feb 27, 2018
checked on Apr 19, 2018
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.