Department of Cell Biology; Department of Pathology
Actins; Adenosine Triphosphatases; Adenosine Triphosphate; Animals; Blotting, Northern; Blotting, Western; Cell Adhesion; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Nucleus; Cell Size; Chromatin; Collagen; Cytoskeletal Proteins; Cytoskeleton; DNA Helicases; DNA, Complementary; Dose-Response Relationship, Drug; Drug Combinations; Focal Adhesions; Gene Expression Regulation; Heterozygote; Humans; Laminin; Mice; Mutation; Neoplasm Metastasis; Nuclear Proteins; Paxillin; Phosphoproteins; Protein Binding; Protein Structure, Tertiary; Proteoglycans; RNA, Messenger; Receptors, Cell Surface; Time Factors; Transcription Factors
Cell Biology | Life Sciences | Medicine and Health Sciences
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.
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Citation: J Cell Sci. 2004 Nov 15;117(Pt 24):5847-54. Link to article on publisher's site