Document Detail


SWI/SNF chromatin remodeling enzyme ATPases promote cell proliferation in normal mammary epithelial cells.
MedLine Citation:
PMID:  20333683     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
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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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  223     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-04-07     Completed Date:  2010-04-21     Revised Date:  2014-01-08    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  667-78     Citation Subset:  IM    
Copyright Information:
(c) 2010 Wiley-Liss, Inc.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphatases / metabolism*
Basement Membrane / drug effects,  metabolism
Cell Cycle / drug effects
Cell Line
Cell Proliferation / drug effects
Chromatin Assembly and Disassembly* / drug effects
DNA Helicases / deficiency,  metabolism*
Doxycycline / pharmacology
Epithelial Cells / cytology*,  enzymology*
Female
Gene Knockdown Techniques
Humans
Mammary Glands, Human / cytology*
Nuclear Proteins / deficiency,  metabolism*
Protein Subunits / metabolism
RNA, Small Interfering / metabolism
RNA, Small Nucleolar / genetics,  metabolism
Transcription Factors / deficiency,  metabolism*
Up-Regulation / drug effects
Grant Support
ID/Acronym/Agency:
P01 CA082834-06/CA/NCI NIH HHS; P01 CA082834-07/CA/NCI NIH HHS; P01 CA082834-08/CA/NCI NIH HHS; P01 CA82834/CA/NCI NIH HHS; P30 DK32520/DK/NIDDK NIH HHS; R01 CA138818/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Nuclear Proteins; 0/Protein Subunits; 0/RNA, Small Interfering; 0/RNA, Small Nucleolar; 0/SMARCA2 protein, human; 0/Transcription Factors; 0/growth arrest specific transcript 5; EC 3.6.1.-/Adenosine Triphosphatases; EC 3.6.1.-/SMARCA4 protein, human; EC 3.6.4.-/DNA Helicases; N12000U13O/Doxycycline
Comments/Corrections

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