| SWI/SNF chromatin remodeling enzyme ATPases promote cell proliferation in normal mammary epithelial cells. | |
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MedLine Citation:
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PMID: 20333683 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Journal of cellular physiology Volume: 223 ISSN: 1097-4652 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-04-07 Completed Date: 2010-04-21 Revised Date: 2012-09-19 |
Medline Journal Info:
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Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: United States |
Other Details:
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Languages: eng Pagination: 667-78 Citation Subset: IM |
Copyright Information:
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(c) 2010 Wiley-Liss, Inc. |
Affiliation:
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Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphatases
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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:
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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 |
| Chemical | |
Reg. No./Substance:
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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; 564-25-0/Doxycycline; EC 3.6.1.-/Adenosine Triphosphatases; EC 3.6.1.-/DNA Helicases; EC 3.6.1.-/SMARCA4 protein, human |
| Comments/Corrections | |
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