{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T23:23:19Z","timestamp":1785367399571,"version":"3.55.0"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,6,14]],"date-time":"2012-06-14T00:00:00Z","timestamp":1339632000000},"content-version":"vor","delay-in-days":44,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotech and App Biochem"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A tumorigenic cell line with estrogen receptor and HER2 expression (ER\/HER2<jats:sup>+<\/jats:sup>), R2N1d, was developed from a human breast epithelial cell type with stem cell characteristics in a growth factor\/hormone\u2010deprived cell culture condition. This study was undertaken to test whether tumor growth and other biological effects could be induced by estrogen in this cell line. The results clearly show that estrogen treatment greatly promoted the tumor growth of R2N1d cells in immune\u2010deficient mice. Estrogen treatment of R2N1d cells <jats:italic>in vitro<\/jats:italic> was also found to induce other phenotypic changes related to breast carcinogenesis, that is, 1) the induction of epithelial\u2013mesenchymal transition (EMT) shown by molecular and functional marker changes; 2) a significant increase of the CD44<jats:sup>high<\/jats:sup>\/CD24<jats:sup>\u2212\/low<\/jats:sup> stem cell population; 3) the enhancement of cell growth rate and colony\u2010forming ability; and 4) the acquisition of metastatic ability, that is, increased cell migration and invasiveness. From these results, we conclude that 1) estrogen could induce EMT and cancer stem cells and promote tumor growth in ER<jats:sup>+<\/jats:sup>\/HER2<jats:sup>+<\/jats:sup> cells known to be derived from human breast epithelial stem cells, and 2) normal stem cells could give rise to cancer stem cells.<\/jats:p>","DOI":"10.1002\/bab.1022","type":"journal-article","created":{"date-parts":[[2012,6,14]],"date-time":"2012-06-14T15:13:56Z","timestamp":1339686836000},"page":"262-267","source":"Crossref","is-referenced-by-count":20,"title":["Promotion of epithelial\u2013mesenchymal transition and tumor growth by 17<i>\u03b2<\/i>\u2010estradiol in an ER<sup>+<\/sup>\/HER2<sup>+<\/sup> cell line derived from human breast epithelial stem cells"],"prefix":"10.1002","volume":"59","author":[{"given":"Kai\u2010Hung","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An\u2010Pei","family":"Kao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ta\u2010Chin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia\u2010Cheng","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsung\u2010Cheng","family":"Kuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,6,14]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0797-730"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03128"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.03.032"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-1343"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-2030"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05372"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2018"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0530291100"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1080"},{"key":"e_1_2_7_11_2","first-page":"5821","volume":"63","author":"Singh S. 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