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

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    Authors
    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.
    UMass Chan Affiliations
    Department of Cell Biology
    Document Type
    Journal Article
    Publication Date
    2010-06-25
    Keywords
    Adenosine 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
    Cell Biology
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    Link to Full Text
    http://dx.doi.org/10.1002/jcp.22072
    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
    DOI
    10.1002/jcp.22072
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/34860
    PubMed ID
    20333683
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1002/jcp.22072
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