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Although the mechanisms responsible for hormone resistance are not completely understood, resistance is associated with alterations in ER\u03b1; overexpression of proteins that interact with the receptor; and hormone\u2010independent activation of the receptor by growth factor signal transduction pathways. Our previous studies show that in estrogen dependent breast cancer cells, activation of the epidermal growth factor signaling pathway increases intracellular calcium which binds to and activates ER\u03b1 through sites in the ligand\u2010binding domain of the receptor and that treatment with extracellular calcium increases the concentration of intracellular calcium which activates ER\u03b1 and induces hormone\u2010independent cell growth. The present study asked whether overexpression of calcium channels contributes to the hormone\u2010independent and \u2010resistant phenotype of breast cancer cells and whether clinically used calcium channel blockers reverse hormone independence and resistance. The results show that hormone\u2010independent and \u2010resistant cells overexpress calcium channels, have high concentrations of intracellular calcium, overexpress estrogen responsive genes and, as expected, grow in the absence of estradiol and that treatment with calcium channel blockers decreased the concentration of intracellular calcium, the expression of estrogen responsive genes and cell growth. More importantly, in hormone\u2010resistant cells, treatment that combined a calcium channel blocker with an antiestrogen reversed resistance to the antiestrogen.<\/jats:p>","DOI":"10.1002\/ijc.33745","type":"journal-article","created":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T11:43:07Z","timestamp":1626867787000},"page":"1817-1827","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Role of calcium in hormone\u2010independent and \u2010resistant breast cancer"],"prefix":"10.1002","volume":"149","author":[{"given":"Kedra","family":"Cyrus","sequence":"first","affiliation":[{"name":"Department of Oncology Georgetown University  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaochu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular &amp; Cellular Biology Georgetown University  Washington District of 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