{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T22:03:57Z","timestamp":1783634637184,"version":"3.55.0"},"reference-count":67,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,1,1]],"date-time":"2004-01-01T00:00:00Z","timestamp":1072915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["K01 CA-79090"],"award-info":[{"award-number":["K01 CA-79090"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2004,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A common phenotype in breast cancer is the expansion of the estrogen receptor\u2010\u03b1 (ER+) cell population and an inappropriate elevation of ER\u03b1 protein, the latter predisposing patients for a poorer prognosis than those with lower levels of the receptor. A tetracycline\u2010inducible ER\u03b1 overexpression model was developed in the MCF\u20107 cell line to assess induction of endogenous gene activation and growth in response to elevations in ER\u03b1 protein. Heightened levels of ER\u03b1 resulted in aberrant promoter occupancy and gene activation in the absence of hormone, which was independent of ligand and AF\u20102 function. This increased receptor activity required the amino\u2010terminal A\/B domain and was not inhibited by tamoxifen, which supports an enhancement of AF\u20101 function, yet was independent of serine\u2010104, 106, and 118 phosphorylation. Ligand\u2010independent transcription was accompanied by an increase in growth in the absence of hormonal stimulation. The results suggest that elevated levels of ER\u03b1 in breast cancer cells can result in activation of receptor transcriptional function in a manner distinct from classical mechanisms that involve ligand binding or growth factor\u2010induced phosphorylation. Further, they describe a potential mechanism whereby increases in ER\u03b1 concentration may provide a proliferative advantage by augmenting ER\u03b1 function regardless of ligand status.\u2014Fowler, A. M., Solodin, N., Preisler\u2010Mashek, M. T., Zhang, P., Lee, A. V., Alarid, E. T. Increases in estrogen receptor\u2010\u03b1 concentration in breast cancer cells promote serine 118\/104\/106\u2010independent AF\u20101 transactivation and growth in the absence of estrogen.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    18, 81\u201393 (2004)\n                  <\/jats:p>","DOI":"10.1096\/fj.03-0038com","type":"journal-article","created":{"date-parts":[[2004,1,12]],"date-time":"2004-01-12T20:16:17Z","timestamp":1073938577000},"page":"81-93","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Increases in estrogen receptor\u2010\u03b1 concentration in breast cancer cells promote serine 118\/104\/106\u2010independent AF\u20101 transactivation and growth in the absence of estrogen"],"prefix":"10.1096","volume":"18","author":[{"given":"Amy M.","family":"Fowler","sequence":"first","affiliation":[{"name":"Department of Physiology University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Solodin","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara T.","family":"Preisler\u2010Mashek","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Breast Center and Department of Medicine Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian V.","family":"Lee","sequence":"additional","affiliation":[{"name":"The Breast Center and Department of Medicine Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine T.","family":"Alarid","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,1]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(87)90307-4"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2964(78)90194-9"},{"key":"e_1_2_5_4_1","first-page":"311","article-title":"Tumour cellularity, oestrogen receptors and prognosis in breast cancer","volume":"9","author":"Black R.","year":"1983","journal-title":"Clin. 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