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Title: Functional Interactions between the Progesterone Receptor and Estrogen Receptor in Breast Cancer Cells
Keywords: breast cancer, MCF-7, 17beta-estradiol, estrogen receptor, progesterone receptor, endocrine therapy resistance
Issue Date: 18-Jul-2006
Citation: ZHENG ZEYI (2006-07-18). Functional Interactions between the Progesterone Receptor and Estrogen Receptor in Breast Cancer Cells. ScholarBank@NUS Repository.
Abstract: Estrogen is known to stimulate tumor growth in estrogen receptor (ER)-positive breast cancers. This study reports a novel antiestrogenic mechanism of recombinant progesterone receptor (PR) in breast cancer cells. Overexpression of PR by stable transfection or adenovirus infection in ER- and PR-positive breast cancer MCF-7 cells revealed that recombinant PR functions antiestrogenically in a ligand-independent manner. Recombinant PR enhances 17beta-estradiol (E2) cellular uptake and thus E2 metabolism, which causes accelerated depletion of E2 and accumulation of E2 antiestrogenic metabolites. Recombinant PR also suppresses liganded ER binding to estrogen response element, thereby directly repressing estrogen-dependent ER transcription activity. Both aforesaid pathways can inhibit estrogen-stimulated MCF-7 cell cycle progression and proliferation. The findings in this study open up a new window for a hitherto unknown functional relationship between PR and ER. The antiestrogenic effect of recombinant PR also provides a potential therapeutic strategy for estrogen-dependent but endocrine-resistant breast cancers.
Appears in Collections:Ph.D Theses (Open)

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