SWI/SNF chromatin remodeling enzyme ATPases promote cell proliferation in normal mammary epithelial cells.

TitleSWI/SNF chromatin remodeling enzyme ATPases promote cell proliferation in normal mammary epithelial cells.
Publication TypeJournal Article
Year of Publication2010
AuthorsCohet N, Stewart KM, Mudhasani R, Asirvatham AJ, Mallappa C, Imbalzano KM, Weaver VM, Imbalzano AN, Nickerson JA
JournalJ Cell Physiol
Volume223
Issue3
Pagination667-78
Date Published2010 Jun
ISSN1097-4652
KeywordsAdenosine Triphosphatases, 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
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.

DOI10.1002/jcp.22072
Alternate JournalJ. Cell. Physiol.
PubMed ID20333683
PubMed Central IDPMC3320666
Grant ListP01 CA082834-06 / CA / NCI NIH HHS / United States
P01 CA082834-07 / CA / NCI NIH HHS / United States
P01 CA082834-08 / CA / NCI NIH HHS / United States
P01 CA82834 / CA / NCI NIH HHS / United States
P30 DK32520 / DK / NIDDK NIH HHS / United States
R01 CA138818 / CA / NCI NIH HHS / United States