{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T19:33:38Z","timestamp":1790451218103,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A body of epidemiological evidence implicates exposure to endocrine disrupting chemicals (EDCs) with increased susceptibility to breast cancer. To evaluate the physiological effects of a suspected EDC <jats:italic>in vivo,<\/jats:italic> we exposed MCF\u20107 breast cancer cells and a patient\u2010derived xenograft (PDX, estrogen receptor positive) to physiological levels of methylparaben (mePB), which is commonly used in personal care products as a preservative. mePB pellets (4.4\u2009\u03bcg per day) led to increased tumor size of MCF\u20107 xenografts and ER<jats:sup>+<\/jats:sup> PDX tumors. mePB has been thought to be a xenoestrogen; however, <jats:italic>in vitro<\/jats:italic> exposure of 10\u2009nM mePB failed to increase MCF\u20107 cell proliferation or induction of canonical estrogen\u2010responsive genes (<jats:italic>pS2<\/jats:italic> and progesterone receptor), in contrast to 17\u03b2\u2010estradiol (E2) treatment. MCF\u20107 and PDX\u2010derived mammospheres exhibited increased size and up\u2010regulation of canonical stem cell markers <jats:italic>ALDH1, NANOG, OCT4<\/jats:italic> and <jats:italic>SOX2<\/jats:italic> when exposed to mePB; these effects were not observed for MDA\u2010MB\u2010231 (ER<jats:sup>\u2212<\/jats:sup>) mammospheres. As tumor\u2010initiating cells (TICs) are also believed to be responsible for chemoresistance, mammospheres were treated with either tamoxifen or the pure anti\u2010estrogen fulvestrant in the presence of mePB. Blocking the estrogenic response was not sufficient to block <jats:italic>NANOG<\/jats:italic> expression in mammospheres, pointing to a non\u2010classic estrogen response or an ER\u2010independent mechanism of mePB promotion of mammosphere activity. Overall, these results suggest that mePB increases breast cancer tumor proliferation through enhanced TIC activity, in part <jats:italic>via<\/jats:italic> regulation of <jats:italic>NANOG,<\/jats:italic> and that mePB may play a direct role in chemoresistance by modulating stem cell activity. Copyright \u00a9 2016 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.3374","type":"journal-article","created":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T07:07:39Z","timestamp":1472713659000},"page":"417-425","source":"Crossref","is-referenced-by-count":45,"title":["Methylparaben stimulates tumor initiating cells in ER+ breast cancer models"],"prefix":"10.1002","volume":"37","author":[{"given":"M. Angeles","family":"Lillo","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery and Biomedical Engineering University of Tennessee Health Science Center  Memphis TN USA"},{"name":"Center for Cancer Research University of Tennessee Health Science Center  Memphis TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cydney","family":"Nichols","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics UCLA  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanel","family":"Perry","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery and Biomedical Engineering University of Tennessee Health Science Center  Memphis TN USA"},{"name":"Center for Cancer Research University of Tennessee Health Science Center  Memphis TN 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