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• W2136833945 abstract "The two isoforms of estrogen receptor (ER) alpha and beta play opposite roles in regulating proliferation and differentiation of breast cancers, with ER-alpha mediating mitogenic effects and ER-beta acting as a tumor suppressor. Emerging data have reported that androgen receptor (AR) activation inhibits ER-positive breast cancer progression mainly by antagonizing ER-alpha signaling. However, to date no studies have specifically evaluated a potential involvement of ER-beta in the inhibitory effects of androgens. ER-beta expression was examined in human breast cancer cell lines using real-time PCR, Western blotting and small interfering RNA (siRNA) assays. Mutagenesis studies, electromobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) analysis were performed to assess the effects of mibolerone/AR on ER-beta promoter activity and binding. In this study, we demonstrate that mibolerone, a synthetic androgen ligand, up-regulates ER-beta mRNA and protein levels in ER-positive breast cancer cells. Transient transfection experiments, using a vector containing the human ER-beta promoter region, show that mibolerone increases basal ER-beta promoter activity. Site-directed mutagenesis and deletion analysis reveal that an androgen response element (ARE), TGTTCT motif located at positions −383 and −377, is critical for mibolerone-induced ER-beta up-regulation in breast cancer cells. This occurs through an increased recruitment of AR to the ARE site within the ER-beta promoter region, along with an enhanced occupancy of RNA polymerase II. Finally, silencing of ER-beta gene expression by RNA interference is able to partially reverse the effects of mibolerone on cell proliferation, p21 and cyclin D1 expression. Collectively, these data provide evidence for a novel mechanism by which activated AR, through an up-regulation of ER-beta gene expression, inhibits breast cancer cell growth." @default.
• W2136833945 created "2016-06-24" @default.
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• W2136833945 date "2014-02-01" @default.
• W2136833945 modified "2023-10-08" @default.
• W2136833945 title "Estrogen receptor beta as a novel target of androgen receptor action in breast cancer cell lines" @default.
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• W2136833945 doi "https://doi.org/10.1186/bcr3619" @default.
• W2136833945 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3978907" @default.
• W2136833945 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24552459" @default.
• W2136833945 hasPublicationYear "2014" @default.
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