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First published online November 10, 2004
doi: 10.1242/10.1242/jcs.01502


Journal of Cell Science 117, 5847-5854 (2004)
Published by The Company of Biologists 2004
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Research Article

Inducible changes in cell size and attachment area due to expression of a mutant SWI/SNF chromatin remodeling enzyme

David A. Hill1,*, Simion Chiosea1,*, Saha Jamaluddin3, Kanaklata Roy1, Andrew H. Fischer2, Douglas D. Boyd3, Jeffrey A. Nickerson1,{ddagger} and Anthony N. Imbalzano1,{ddagger}

1 Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
2 Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
3 Department of Cancer Biology, The University of Texas-MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA

{ddagger} Authors for correspondence (e-mail: jeffrey.nickerson{at}umassmed.edu; anthony.imbalzano{at}umassmed.edu)

Accepted 19 August 2004

The SWI/SNF enzymes belong to a family of ATP-dependent chromatin remodeling enzymes that have been functionally implicated in gene regulation, development, differentiation and oncogenesis. BRG1, the catalytic core subunit of some of the SWI/SNF enzymes, can interact with known tumor suppressor proteins and can act as a tumor suppressor itself. We report that cells that inducibly express ATPase-deficient versions of BRG1 increase in cell volume, area of attachment and nuclear size upon expression of the mutant BRG1 protein. Examination of focal adhesions reveals qualitative changes in paxillin distribution but no difference in the actin cytoskeletal structure. Increases in cell size and shape correlate with over-expression of two integrins and the urokinase-type plasminogen activator receptor (uPAR), which is also involved in cell adhesion and is often over-expressed in metastatic cancer cells. These findings demonstrate that gene expression pathways affected by chromatin remodeling enzymes can regulate the physical dimensions of mammalian cell morphology.

Key words: Cell size and shape, Nuclear size, SWI/SNF, BRG1, Chromatin remodeling




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