SWI/SNF chromatin remodeling enzyme ATPases promote cell proliferation in normal mammary epithelial cells |
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Authors: | Nathalie Cohet Kathleen M Stewart Rajini Mudhasani Ananthi J Asirvatham Chandrashekara Mallappa Karen M Imbalzano Valerie M Weaver Anthony N Imbalzano Jeffrey A Nickerson |
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Institution: | 1. Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts;2. Department of Surgery, Center for Bioengineering and Tissue Regeneration, University of California at San Francisco, San Francisco, California |
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Abstract: | The ATPase subunits of the SWI/SNF chromatin remodeling enzymes, Brahma (BRM) and Brahma‐related gene 1 (BRG1), can induce cell cycle arrest in BRM and BRG1 deficient tumor cell lines, and mice heterozygous for Brg1 are pre‐disposed to breast tumors, implicating loss of BRG1 as a mechanism for unregulated cell proliferation. To test the hypothesis that loss of BRG1 can contribute to breast cancer, we utilized RNA interference to reduce the amounts of BRM or BRG1 protein in the nonmalignant mammary epithelial cell line, MCF‐10A. When grown in reconstituted basement membrane (rBM), these cells develop into acini that resemble the lobes of normal breast tissue. Contrary to expectations, knockdown of either BRM or BRG1 resulted in an inhibition of cell proliferation in monolayer cultures. This inhibition was strikingly enhanced in three‐dimensional rBM culture, although some BRM‐depleted cells were later able to resume proliferation. Cells did not arrest in any specific stage of the cell cycle; instead, the cell cycle length increased by approximately 50%. Thus, SWI/SNF ATPases promote cell cycle progression in nonmalignant mammary epithelial cells. J. Cell. Physiol. 223:667–678, 2010. © 2010 Wiley‐Liss, Inc. |
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