{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:59:10Z","timestamp":1787061550174,"version":"build-2736575974"},"reference-count":41,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:00:00Z","timestamp":1707264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Center for Biomedical Research, Oakland University William Beaumont School of Medicine Student Research Grant"},{"name":"Oakland University Provost Undergraduate Student Research Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Selective estrogen receptor modulators (SERMs) are steroid analogs with dual functionality, acting as partial estrogen receptor agonists to preserve postmenopausal bone density and as estrogen receptor antagonists in breast tissue. Bazedoxifene acetate (BZA) is an FDA-approved, third-generation SERM used in the treatment of osteoporosis in women. It demonstrates potential as a therapeutic option for breast cancer patients undergoing endocrine therapy. Our study aimed to assess BZA\u2019s effects on Estrogen Receptor Alpha (ER\u03b1) and tumor suppressor gene BRCA1 in T-47D and MCF-7 breast cancer cells, using Western blots, cellular viability, apoptosis assays, and RT-qPCR. Cells were cultured in 5% charcoal-stripped fetal bovine serum for six days to deplete endogenous steroids. Following a 24 h exposure to 2 \u00b5M BZA (optimal concentration determined from 1 nM\u20132 \u00b5M studies), Western blot analyses revealed reduced ER\u03b1 and BRCA1 protein levels in both cell lines. ER\u03b1 decreased by 48\u201363% and BRCA1 by 61\u201364%, indicating sensitivity to antiestrogens. Cytolocalization of ER\u03b1 and BRCA1 remained unchanged after BZA and 17-\u03b2-estradiol (E2) treatment. ESR1 mRNA expression correlated with Western blot findings. Image cytometric analysis using the stain, propidium iodide, detected decreased cellular proliferation in T-47D and MCF-7 cells following a 6-day treatment ranging from 1 nM to 2 \u00b5M BZA. BZA treatment alone led to a tenfold reduction in cellular proliferation compared to estrogen-treated cells, suggesting antiproliferative effects. Understanding BZA\u2019s modulation of BRCA1 and ER\u03b1, along with their mechanistic interactions, is vital for comprehending its impact on breast cancer tumor suppressors and hormone receptors.<\/jats:p>","DOI":"10.3390\/cancers16040699","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T03:47:09Z","timestamp":1707277629000},"page":"699","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Modulation of Estrogen Receptor Alpha (ER\u03b1) and Tumor Suppressor Gene BRCA1 in Breast Cancer Cells by Bazedoxifene Acetate (BZA)"],"prefix":"10.3390","volume":"16","author":[{"given":"Monica","family":"Szmyd","sequence":"first","affiliation":[{"name":"Department of Clinical and Diagnostic Sciences, School of Health Sciences, Oakland University, Rochester, MI 48309, USA"},{"name":"Department of Foundational Medical Sciences, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, USA"},{"name":"Institute of Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI 48309, USA"},{"name":"Center for Biomedical Research, Oakland University, Rochester, MI 48309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisha","family":"Zanib","sequence":"additional","affiliation":[{"name":"Department of Clinical and Diagnostic Sciences, School of Health Sciences, Oakland University, Rochester, MI 48309, USA"},{"name":"Institute of Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI 48309, USA"},{"name":"Center for Biomedical Research, Oakland University, Rochester, MI 48309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Behlow","sequence":"additional","affiliation":[{"name":"Department of Clinical and Diagnostic Sciences, School of Health Sciences, Oakland University, Rochester, MI 48309, USA"},{"name":"Institute of Stem Cell and Regenerative Medicine, Oakland 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Rochester, MI 48309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katelyn","family":"Farrar","sequence":"additional","affiliation":[{"name":"Department of Clinical and Diagnostic Sciences, School of Health Sciences, Oakland University, Rochester, MI 48309, USA"},{"name":"Institute of Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI 48309, USA"},{"name":"Center for Biomedical Research, Oakland University, Rochester, MI 48309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumi","family":"Dinda","sequence":"additional","affiliation":[{"name":"Department of Clinical and Diagnostic Sciences, School of Health Sciences, Oakland University, Rochester, MI 48309, USA"},{"name":"Institute of Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI 48309, USA"},{"name":"Center for Biomedical Research, Oakland University, Rochester, MI 48309, 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