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

David N. Reisman, Matthew W. Strobeck, Bryan L. Betz, Janiece Sciariotta, William Funkhouser, Christian Murchardt, Moshe Yaniv, Lawrence (Larry) Sherman, Erik S. Knudsen, Bernard E. Weissman

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1196-1207
Number of pages12
JournalOncogene
Volume21
Issue number8
DOIs
StatePublished - Feb 14 2002
Externally publishedYes

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Keywords

  • CD44
  • Chromatin remodeling
  • RB
  • Tumor suppression

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Reisman, D. N., Strobeck, M. W., Betz, B. L., Sciariotta, J., Funkhouser, W., Murchardt, C., Yaniv, M., Sherman, L. L., Knudsen, E. S., & Weissman, B. E. (2002). Concomitant down-regulation of BRM and BRG1 in human tumor cell lines: Differential effects on RB-mediated growth arrest vs CD44 expression. Oncogene, 21(8), 1196-1207. https://doi.org/10.1038/sj/onc/1205188