Modulation of Runx2 activity by estrogen receptor-α: Implications for osteoporosis and breast cancer

Omar Khalid, Sanjeev K. Baniwal, Daniel J. Purcell, Nathalie Leclerc, Yankel Gabet, Michael R. Stallcup, Gerhard A. Coetzee, Baruch Frenkel

Research output: Contribution to journalArticlepeer-review


The transcription factors Runx2 and estrogen receptor-α (ERα) 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 ERα strongly interacted with Runx2 directly through its DNA-binding domain and only indirectly through its N-terminal and ligand-binding domains. Runx2's amino acids 417-514, encompassing activation domain 3 and the nuclear matrix targeting sequence, were sufficient for interaction with ERα's DNA-binding domain. As a consequence of the interaction, Runx2's 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 ERα and Runx2 target genes. Selective ER modulators (SERM) induced ERα-Runx2 interactions but led to various functional outcomes. The regulation of Runx2 by ERα may play key roles in osteoblast and breast epithelial cell growth and differentiation; hence, modulation of Runx2 by native and synthetic ERα ligands offers new avenues in selective ER modulator evaluation and development.

Original languageEnglish
Pages (from-to)5984-5995
Number of pages12
Issue number12
StatePublished - Dec 2008
Externally publishedYes


Dive into the research topics of 'Modulation of Runx2 activity by estrogen receptor-α: Implications for osteoporosis and breast cancer'. Together they form a unique fingerprint.

Cite this