SWI/SNF Chromatin Remodeling Enzyme ATPases Promote Cell Proliferation in Normal Mammary Epithelial Cells

Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Journal of Cellular Physiology (Impact Factor: 3.87). 01/2010; 223(3):667-78. DOI: 10.1002/jcp.22072
Source: PubMed

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.

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Available from: Jeffrey A Nickerson, Jul 28, 2015
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    • "In agreement with our results, neither enhanced proliferation nor decreased apoptosis have been demonstrated upon application of SMARCA4-specific smallinterfering RNA in the literature to date. In contrast, in normal mammary epithelial cells, SMARCA4 knockdown even inhibited cell proliferation (Cohet et al., 2010). Given the fundamental function of SMARCA4 in cellular transcription, the precise cellular context leading to its tumor suppressive effect remains to be elucidated. "
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