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Cancer Res. 2011 Mar 15;71(6):2118-28. doi: 10.1158/0008-5472.CAN-10-2426. Epub 2011 Jan 31.

CARM1 is an important determinant of ERα-dependent breast cancer cell differentiation and proliferation in breast cancer cells.

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  • 1McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wisconsin 53706, USA.

Abstract

Breast cancers with estrogen receptor α (ERα) expression are often more differentiated histologically than ERα-negative tumors, but the reasons for this difference are poorly understood. One possible explanation is that transcriptional cofactors associated with ERα determine the expression of genes which promote a more differentiated phenotype. In this study, we identify one such cofactor as coactivator-associated arginine methyltransferase 1 (CARM1), a unique coactivator of ERα that can simultaneously block cell proliferation and induce differentiation through global regulation of ERα-regulated genes. CARM1 was evidenced as an ERα coactivator in cell-based assays, gene expression microarrays, and mouse xenograft models. In human breast tumors, CARM1 expression positively correlated with ERα levels in ER-positive tumors but was inversely correlated with tumor grade. Our findings suggest that coexpression of CARM1 and ERα may provide a better biomarker of well-differentiated breast cancer. Furthermore, our findings define an important functional role of this histone arginine methyltransferase in reprogramming ERα-regulated cellular processes, implicating CARM1 as a putative epigenetic target in ER-positive breast cancers.

©2011 AACR.

PMID:
21282336
[PubMed - indexed for MEDLINE]
PMCID:
PMC3076802
Free PMC Article

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