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

120 Citations (Scopus)

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 - Jan 1 2002
Externally publishedYes

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Chromatin Assembly and Disassembly
Cell Cycle Checkpoints
Tumor Cell Line
Down-Regulation
Cyclin A
Growth
Transfection
Gene Expression
Messenger RNA
Proteins

Keywords

  • CD44
  • Chromatin remodeling
  • RB
  • Tumor suppression

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Reisman, D. N., Strobeck, M. W., Betz, B. L., Sciariotta, J., Funkhouser, W., Murchardt, C., ... 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

Concomitant down-regulation of BRM and BRG1 in human tumor cell lines : Differential effects on RB-mediated growth arrest vs CD44 expression. / Reisman, David N.; Strobeck, Matthew W.; Betz, Bryan L.; Sciariotta, Janiece; Funkhouser, William; Murchardt, Christian; Yaniv, Moshe; Sherman, Lawrence (Larry); Knudsen, Erik S.; Weissman, Bernard E.

In: Oncogene, Vol. 21, No. 8, 01.01.2002, p. 1196-1207.

Research output: Contribution to journalArticle

Reisman, DN, Strobeck, MW, Betz, BL, Sciariotta, J, Funkhouser, W, Murchardt, C, Yaniv, M, Sherman, LL, Knudsen, ES & Weissman, BE 2002, 'Concomitant down-regulation of BRM and BRG1 in human tumor cell lines: Differential effects on RB-mediated growth arrest vs CD44 expression', Oncogene, vol. 21, no. 8, pp. 1196-1207. https://doi.org/10.1038/sj.onc.1205188
Reisman, David N. ; Strobeck, Matthew W. ; Betz, Bryan L. ; Sciariotta, Janiece ; Funkhouser, William ; Murchardt, Christian ; Yaniv, Moshe ; Sherman, Lawrence (Larry) ; Knudsen, Erik S. ; Weissman, Bernard E. / Concomitant down-regulation of BRM and BRG1 in human tumor cell lines : Differential effects on RB-mediated growth arrest vs CD44 expression. In: Oncogene. 2002 ; Vol. 21, No. 8. pp. 1196-1207.
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