{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T02:41:02Z","timestamp":1788748862333,"version":"build-2803163510"},"reference-count":52,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,12,1]]},"abstract":"<jats:p>The transcription factors Runx2 and estrogen receptor-\u03b1 (ER\u03b1) are involved in numerous normal and disease processes, including postmenopausal osteoporosis and breast cancer. Using indirect immunofluorescence microscopy and pull-down techniques, we found them to colocalize and form complexes in a ligand-dependent manner. Estradiol-bound ER\u03b1 strongly interacted with Runx2 directly through its DNA-binding domain and only indirectly through its N-terminal and ligand-binding domains. Runx2\u2019s amino acids 417\u2013514, encompassing activation domain 3 and the nuclear matrix targeting sequence, were sufficient for interaction with ER\u03b1\u2019s DNA-binding domain. As a consequence of the interaction, Runx2\u2019s transcriptional activation activity was strongly repressed, as shown by reporter assays in COS7 cells, breast cancer cells, and late-stage MC3T3-E1 osteoblast cultures. Metaanalysis of gene expression in 779 breast cancer biopsies indicated negative correlation between the expression of ER\u03b1 and Runx2 target genes. Selective ER modulators (SERM) induced ER\u03b1-Runx2 interactions but led to various functional outcomes. The regulation of Runx2 by ER\u03b1 may play key roles in osteoblast and breast epithelial cell growth and differentiation; hence, modulation of Runx2 by native and synthetic ER\u03b1 ligands offers new avenues in selective ER modulator evaluation and development.<\/jats:p>","DOI":"10.1210\/en.2008-0680","type":"journal-article","created":{"date-parts":[[2008,8,28]],"date-time":"2008-08-28T20:46:35Z","timestamp":1219956395000},"page":"5984-5995","source":"Crossref","is-referenced-by-count":73,"title":["Modulation of Runx2 Activity by Estrogen Receptor-\u03b1: Implications for Osteoporosis and Breast Cancer"],"prefix":"10.1210","volume":"149","author":[{"given":"Omar","family":"Khalid","sequence":"first","affiliation":[{"name":"From Departments of Urology (O.K., Y.G., G.A.C.), Keck School of Medicine, University of Southern California, Los Angeles, California 90033"},{"name":"Preventive Medicine (O.K., G.A.C.), Keck School of Medicine, University of Southern California, Los Angeles, 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