{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:43:14Z","timestamp":1790635394902,"version":"4.1.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"12","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:p>Acquired resistance to aromatase inhibitors (AIs) is a significant clinical issue in endocrine therapy for estrogen receptor (ER) positive breast cancer which accounts for the majority of breast cancer. Despite estrogen production being suppressed, ER\u03b1 signaling remains active and plays a key role in most AI-resistant breast tumors. Here, we found that amphiregulin (AREG), an ER\u03b1 transcriptional target and EGF receptor (EGFR) ligand, is crucial for maintaining ER\u03b1 expression and signaling in acquired AI-resistant breast cancer cells. AREG was deregulated and critical for cell viability in ER+ AI-resistant breast cancer cells, and ectopic expression of AREG in hormone responsive breast cancer cells promoted endocrine resistance. RNA-sequencing and reverse phase protein array analyses revealed that AREG maintains ER\u03b1 expression and signaling by activation of PI3K\/Akt\/mTOR signaling and upregulation of forkhead box M1 (FOXM1) and serum- and glucocorticoid-inducible kinase 3 (SGK3) expression. Our study uncovers a previously unappreciated role of AREG in maintaining ER\u03b1 expression and signaling, and establishes the AREG-ER\u03b1 crosstalk as a driver of acquired AI resistance in breast cancer.<\/jats:p>","DOI":"10.1530\/erc-20-0258","type":"journal-article","created":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T13:50:48Z","timestamp":1601560248000},"page":"671-683","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":10,"title":["Amphiregulin retains ER\u03b1 expression in acquired aromatase inhibitor resistant breast cancer cells"],"prefix":"10.1530","volume":"27","author":[{"given":"Yuanzhong","family":"Wang","sequence":"first","affiliation":[{"name":"1Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Dun Tony","family":"Tzeng","sequence":"additional","affiliation":[{"name":"1Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, California, USA"},{"name":"2Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Chang","sequence":"additional","affiliation":[{"name":"1Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"1Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiuan","family":"Chen","sequence":"additional","affiliation":[{"name":"1Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/27\/12\/ERC-20-0258.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/27\/12\/ERC-20-0258.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:55:45Z","timestamp":1784555745000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/erc\/article\/27\/12\/671-683\/25393"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":0,"journal-issue":{"issue":"12"},"URL":"https:\/\/doi.org\/10.1530\/erc-20-0258","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12]]}}}