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In contrast to its transcriptional repression in all other adult normal tissues, PLAC1 is frequently activated and highly expressed in a variety of human cancers, in particular breast cancer, where it associates with estrogen receptor \u03b1 (ER\u03b1) positivity. In a previous study, we showed that ER\u03b1-signaling in breast cancer cells transactivates<jats:italic>PLAC1<\/jats:italic>expression in a non-classical pathway. As the members of the p160\/nuclear receptor co-activator (NCOA) family, NCOA1, NCOA2 and NCOA3 are known to be overexpressed in breast cancer and essentially involved in estrogen-mediated cancer cell proliferation we asked if these proteins are involved in the ER\u03b1-mediated transactivation of<jats:italic>PLAC1<\/jats:italic>in breast cancer cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Applying quantitative real-time RT-PCR (qRT-PCR), Western Blot analysis and chromatin immunoprecipitation, we analyzed the involvement of NCOA1, NCOA2, NCOA3 in the ER\u03b1-mediated transactivation of<jats:italic>PLAC1<\/jats:italic>in the breast cancer cell lines MCF-7 and SK-BR-3. RNAi-mediated silencing of NCOA3, qRT-PCR, Western blot analysis and ER\u03b1 activation assays were used to examine the role of NCOA3 in the ER\u03b1-mediated regulation of PLAC1 in further detail. Transcript expression of<jats:italic>NCOA3<\/jats:italic>and<jats:italic>PLAC1<\/jats:italic>in 48 human breast cancer samples was examined by qRT-PCR and statistical analysis was performed using Student\u2019s<jats:italic>t<\/jats:italic>-test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We detected selective recruitment of NCOA3 but not NCOA1 or NCOA2 to the<jats:italic>PLAC1<\/jats:italic>promoter only in ER\u03b1-positive MCF-7 cells but not in ER\u03b1-negative SK-BR-3 breast cancer cells. In addition, we demonstrate that silencing of NCOA3 results in a remarkable decrease of PLAC1 expression levels in MCF-7 cells which cannot be restored by treatment with estradiol (E<jats:sub>2<\/jats:sub>). Moreover, significant higher transcript levels of<jats:italic>PLAC1<\/jats:italic>were found only in ER\u03b1-positive human breast cancer samples which also show a<jats:italic>NCOA3<\/jats:italic>overexpression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this study, we identified NCOA3 as a selective co-activator of ER\u03b1-mediated transactivation of<jats:italic>PLAC1<\/jats:italic>in MCF-7 breast cancer cells. Our data introduce<jats:italic>PLAC1<\/jats:italic>as novel target gene of NCOA3 in breast cancer, supporting the important role of both factors in breast cancer biology.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2407-13-570","type":"journal-article","created":{"date-parts":[[2013,12,5]],"date-time":"2013-12-05T01:27:16Z","timestamp":1386206836000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["NCOA3 is a selective co-activator of estrogen receptor \u03b1-mediated transactivation of PLAC1 in MCF-7 breast cancer cells"],"prefix":"10.1186","volume":"13","author":[{"given":"Meike","family":"Wagner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Koslowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Paret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zlem","family":"T\u00fcreci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugur","family":"Sahin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,12,4]]},"reference":[{"key":"4194_CR1","doi-asserted-by":"publisher","first-page":"9528","DOI":"10.1158\/0008-5472.CAN-07-1350","volume":"67","author":"M Koslowski","year":"2007","unstructured":"Koslowski M, Sahin U, Mitnacht-Kraus R, Seitz G, Huber C, Tureci O: A placenta-specific gene ectopically activated in many human cancers is essentially involved in malignant cell processes. 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