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  • Original Paper
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Concomitant down-regulation of BRM and BRG1 in human tumor cell lines: differential effects on RB-mediated growth arrest vs CD44 expression

Oncogene volume 21, pages 1196–1207 (2002)Cite this article

Abstract

Mammalian cells express two homologs of the SWI2 subunit of the SWI/SNF chromatin-remodeling complex called BRG1 and BRM. Whether the SWI/SNF complexes formed by these two subunits perform identical or different functions remains an important question. In this report, we show concomitant down-regulation of BRG1 and BRM in six human tumor cell lines. This down-regulation occurs at the level of mRNA abundance. We tested whether BRM could affect aberrant cellular functions attributed to BRG1 in tumor cell lines. By transient transfection, we found that BRM can restore RB-mediated cell cycle arrest, induce expression of CD44 protein and suppress Cyclin A expression. Therefore, BRM may be consistently down-regulated with BRG1 during neoplastic progression because they share some redundant functions. However, assorted tissues from BRM null/BRG1-positive mice lack CD44 expression, suggesting that BRM-containing SWI/SNF complexes regulate expression of this gene under physiological conditions. Our studies further define the mechanism by which chromatin-remodeling complexes participate in RB-mediated cell cycle arrest and provide additional novel evidence that the functions of SWI/SNF complexes containing BRG1 or BRM are not completely interchangeable.

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Acknowledgements

We thank Dr Al Baldwin for critical reading of the manuscript, Dr Weidong Wang for the generous gift of the BRG1 and BRM expression vectors and the polyclonal antisera to BAF47, BAF180, BAF53, and BRG1 and the help of Dr Terry Magnuson, Dr Scott Bultman, Tom Gebuhr and Della Yee for the BRM-deficient mouse tissues. This work was supported by grants from the National Institutes of Health CA63176 (BE Weissman), DE/CA12355 (BE Weissman), NIH NS39550 (LS Sherman), a supplement to Promote Research Collaborations for ES Knudsen and BE Weissman, the Ruth Lyons Cancer Research Challenge Fund (ES Knudsen/LS Sherman) and CA82525 (ES Knudsen). Dr David Reisman received support from the National Institutes of Health T32CA09156 and the Kemper Foundation, University of Texas Medical Branch, Galveston, TX, USA.

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Authors and Affiliations

  1. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, 275997295, North Carolina, NC, USA

    David N Reisman & Bernard E Weissman

  2. Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, 27599-7525, North Caroline, NC, USA

    Bryan L Betz, Janiece Sciariotta, William Funkhouser Jr & Bernard E Weissman

  3. Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati College of Medicine, Cincinnati, 45267-0521, Ohio, OH, USA

    Matthew W Strobeck, Larry S Sherman & Erik S Knudsen

  4. Unitè des Virus Oncogènes, URA 1644 du CNRS, Dèpartement des Biotechnologies, Institut Pasteur, Paris, 75724, Cedex 15, France

    Christian Murchardt & Moshe Yaniv

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  1. David N Reisman
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Correspondence to Bernard E Weissman.

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Reisman, D., Strobeck, M., Betz, B. et al. Concomitant down-regulation of BRM and BRG1 in human tumor cell lines: differential effects on RB-mediated growth arrest vs CD44 expression. Oncogene 21, 1196–1207 (2002). https://doi.org/10.1038/sj.onc.1205188

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