{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T21:22:59Z","timestamp":1791062579724,"version":"4.1.0"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"17","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,8,14]]},"abstract":"<jats:p>Mutational inactivation of BRCA1 confers a cumulative lifetime risk\n of breast and ovarian cancers. However, the underlying basis for the\n tissue-restricted tumor-suppressive properties of BRCA1 remains poorly\n defined. Here we show that BRCA1 mediates ligand-independent\n transcriptional repression of the estrogen receptor \u03b1 (ER\u03b1), a\n principal determinant of the growth, differentiation, and normal\n functional status of breasts and ovaries. In Brca1-null mouse embryo\n fibroblasts and BRCA1-deficient human ovarian cancer cells, ER\u03b1\n exhibited ligand-independent transcriptional activity that was not\n observed in Brca1-proficient cells. Ectopic expression in\n Brca1-deficient cells of wild-type BRCA1, but not clinically validated\n BRCA1 missense mutants, restored ligand-independent repression of ER\u03b1\n in a manner dependent upon apparent histone deacetylase activity. In\n estrogen-dependent human breast cancer cells, chromatin\n immunoprecipitation analysis revealed the association of BRCA1 with\n ER\u03b1 at endogenous estrogen-response elements before, but\n not after estrogen stimulation. Collectively, these results reveal\n BRCA1 to be a ligand-reversible barrier to transcriptional activation\n by unliganded promoter-bound ER\u03b1 and suggest a possible mechanism by\n which functional inactivation of BRCA1 could promote\n tumorigenesis through inappropriate hormonal regulation of mammary and\n ovarian epithelial cell proliferation.<\/jats:p>","DOI":"10.1073\/pnas.171174298","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:34:10Z","timestamp":1027679650000},"page":"9587-9592","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":165,"title":["BRCA1 mediates ligand-independent transcriptional repression of the estrogen receptor"],"prefix":"10.1073","volume":"98","author":[{"given":"Lei","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Institute of Biotechnology,\r University of Texas Health Science Center, 15355 Lambda Drive, San\r Antonio, TX 78245; and Laboratory of Molecular\r Carcinogenesis, National Institute of Environmental Health Sciences,\r Research Triangle Park, NC 27709"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lois A.","family":"Annab","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Institute of Biotechnology,\r University of Texas Health Science Center, 15355 Lambda Drive, San\r Antonio, TX 78245; and Laboratory of Molecular\r Carcinogenesis, National Institute of Environmental Health Sciences,\r Research Triangle Park, NC 27709"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia A.","family":"Afshari","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Institute of Biotechnology,\r University of Texas Health Science Center, 15355 Lambda Drive, San\r Antonio, TX 78245; and Laboratory of Molecular\r Carcinogenesis, National Institute of Environmental Health Sciences,\r Research Triangle Park, NC 27709"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Hwa","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Institute of Biotechnology,\r University of Texas Health Science Center, 15355 Lambda Drive, San\r Antonio, TX 78245; and Laboratory of Molecular\r Carcinogenesis, National Institute of Environmental Health Sciences,\r Research Triangle Park, NC 27709"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Boyer","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Institute of Biotechnology,\r University of Texas Health Science Center, 15355 Lambda Drive, San\r Antonio, TX 78245; and Laboratory of Molecular\r Carcinogenesis, National Institute of Environmental Health Sciences,\r Research Triangle Park, NC 27709"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,8,7]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.14.1126"},{"key":"e_1_3_3_2_2","first-page":"1222","volume":"57","author":"Tirkkonen M","year":"1997","unstructured":"M Tirkkonen, O Johannsson, B A Agnarsson, H Olsson, S Ingvarsson, R Karhu, M Tanner, J Isola, R B Barkardottir, A Borg, O Kallioniemi Cancer Res 57, 1222\u20131227 (1997).","journal-title":"Cancer Res"},{"key":"e_1_3_3_3_2","first-page":"3237","volume":"58","author":"Tomlinson G E","year":"1998","unstructured":"G E Tomlinson, T T Chen, V A Stastny, A K Virmani, M A Spillman, V Tonk, J L Blum, N R Schneider, I I Wistuba, J W Shay, et al. 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