{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T23:48:29Z","timestamp":1779061709415,"version":"3.51.4"},"reference-count":63,"publisher":"American Society for Cell Biology (ASCB)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:p>Estrogen receptor (ER)\u03b1 is a critical target of therapeutic strategies to control the proliferation of hormone-dependent breast cancers. Preferred clinical options have significant adverse side effects that can lead to treatment resistance due to the persistence of active estrogen receptors. We have established the cellular mechanism by which indole-3-carbinol (I3C), a promising anticancer phytochemical from Brassica vegetables, ablates ER\u03b1 expression, and we have uncovered a critical role for the GATA3 transcription factor in this indole-regulated cascade. I3C-dependent activation of the aryl hydrocarbon receptor (AhR) initiates Rbx-1 E3 ligase-mediated ubiquitination and proteasomal degradation of ER\u03b1 protein. I3C inhibits endogenous binding of ER\u03b1 with the 3\u2032-enhancer region of GATA3 and disrupts endogenous GATA3 interactions with the ER\u03b1 promoter, leading to a loss of GATA3 and ER\u03b1 expression. Ectopic expression of GATA3 has no effect on I3C-induced ER\u03b1 protein degradation but does prevent I3C inhibition of ER\u03b1 promoter activity, demonstrating the importance of GATA3 in this I3C-triggered cascade. Our preclinical results implicate I3C as a novel anticancer agent in human cancers that coexpress ER\u03b1, GATA3, and AhR, a combination found in a large percentage of breast cancers but not in other critical ER\u03b1 target tissues essential to patient health.<\/jats:p>","DOI":"10.1091\/mbc.e09-08-0689","type":"journal-article","created":{"date-parts":[[2010,2,4]],"date-time":"2010-02-04T02:11:14Z","timestamp":1265249474000},"page":"1166-1177","source":"Crossref","is-referenced-by-count":69,"title":["Indole-3-Carbinol Triggers Aryl Hydrocarbon Receptor-dependent Estrogen Receptor (ER)\u03b1 Protein Degradation in Breast Cancer Cells Disrupting an ER\u03b1-GATA3 Transcriptional Cross-Regulatory Loop"],"prefix":"10.1091","volume":"21","author":[{"given":"Crystal N.","family":"Marconett","sequence":"first","affiliation":[{"name":"Departments of *Molecular and Cell Biology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shyam N.","family":"Sundar","sequence":"additional","affiliation":[{"name":"Departments of *Molecular and Cell Biology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin M.","family":"Poindexter","sequence":"additional","affiliation":[{"name":"Departments of *Molecular and Cell Biology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa R.","family":"Stueve","sequence":"additional","affiliation":[{"name":"Departments of *Molecular and Cell Biology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonard F.","family":"Bjeldanes","sequence":"additional","affiliation":[{"name":"Nutritional Sciences and Toxicology, University of California\u2013Berkeley, CA 94720"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary L.","family":"Firestone","sequence":"additional","affiliation":[{"name":"Departments of *Molecular and Cell Biology and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1076","reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.1242\/dev.026443","volume":"135","author":"Afouda B. 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