SWI/SNF chromatin remodeling enzyme ATPases promote cell proliferation in normal mammary epithelial cells
Cohet, Nathalie ; Stewart, Kathleen M. ; Mudhasani, Rajini R. ; Asirvatham, Ananthi J. ; Mallappa, Chandrashekara ; Imbalzano, Karen M. ; Weaver, Valerie M. ; Imbalzano, Anthony N. ; Nickerson, Jeffrey A.
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Keywords
Basement Membrane
Cell Cycle
Cell Line
Cell Proliferation
*Chromatin Assembly and Disassembly
DNA Helicases
Doxycycline
Epithelial Cells
Female
Gene Knockdown Techniques
Humans
Mammary Glands, Human
Nuclear Proteins
Protein Subunits
RNA, Small Interfering
RNA, Small Nucleolar
Transcription Factors
Up-Regulation
Cell Biology
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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.
Source
J Cell Physiol. 2010 Jun;223(3):667-78. Link to article on publisher's site