{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:52:30Z","timestamp":1791150750467,"version":"4.1.0"},"reference-count":41,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Metastasis of breast cancer to bone occurs with advanced disease and produces substantial morbidity. Secretion of PTH-related peptide (PTHrP) from breast cancer cells is thought to play a key role in osteolytic metastases and is increased by transforming growth factor-\u03b2 (TGF\u03b2), which is released from resorbed bone. Elevated extracellular calcium (Cao2+) also stimulates PTHrP secretion from various normal and malignant cells, an action that could potentially be mediated by the Cao2+-sensing receptor (CaR) originally cloned from the parathyroid gland. Indeed, we previously showed that both normal breast ductal epithelial cells and primary breast cancers express the CaR. In this study we investigated whether the MCF-7 and MDA-MB-231 human breast cancer cell lines express the CaR and whether CaR agonists modulate PTHrP secretion. Northern blot analysis and RT-PCR revealed bona fide CaR transcripts, and immunocytochemistry and Western analysis with a specific anti-CaR antiserum demonstrated CaR protein expression in both breast cancer cell lines. Furthermore, elevated Cao2+ and the polycationic CaR agonists, neomycin and spermine, stimulated PTHrP secretion dose dependently, with maximal, 2.1- to 2.3-fold stimulation. In addition, pretreatment of MDA-MB-231 cells overnight with TGF\u03b21 (0.2, 1, or 5 ng\/ml) augmented both basal and high Cao2+-stimulated PTHrP secretion. Thus, in PTHrP-secreting breast cancers metastatic to bone, the CaR could potentially participate in a vicious cycle in which PTHrP-induced bone resorption raises the levels of Cao2+ and TGF\u03b2 within the bony microenvironment, which then act in concert to evoke further PTHrP release and worsening osteolysis.<\/jats:p>","DOI":"10.1210\/endo.141.12.7849","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T16:10:53Z","timestamp":1389197453000},"page":"4357-4364","source":"Crossref","is-referenced-by-count":182,"title":["Extracellular Calcium-Sensing Receptor Expression and Its Potential Role in Regulating Parathyroid Hormone-Related Peptide Secretion in Human Breast Cancer Cell Lines*"],"prefix":"10.1210","volume":"141","author":[{"given":"Jennifer L.","family":"Sanders","sequence":"first","affiliation":[{"name":"Endocrine-Hypertension Division and Membrane Biology Program, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naibedya","family":"Chattopadhyay","sequence":"additional","affiliation":[{"name":"Endocrine-Hypertension Division and Membrane Biology Program, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Kifor","sequence":"additional","affiliation":[{"name":"Endocrine-Hypertension Division and Membrane Biology Program, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Endocrine-Hypertension Division and Membrane Biology Program, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert R.","family":"Butters","sequence":"additional","affiliation":[{"name":"Endocrine-Hypertension Division and Membrane Biology Program, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward M.","family":"Brown","sequence":"additional","affiliation":[{"name":"Endocrine-Hypertension Division and Membrane Biology Program, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071621282933300_R1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/canjclin.44.1.7","article-title":"Cancer statistics, 1994.","volume":"44","author":"Boring","year":"1994","journal-title":"CA Cancer J 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