The BRG-1 Subunit of the SWI/SNF Complex Regulates CD44 Expression

Matthew W. Strobeck, Marc F. DeCristofaro, Fatima Banine, Bernard E. Weissman, Larry S. Sherman, Erik S. Knudsen

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Aberrant regulation of CD44, a transmembrane glycoprotein, has been implicated in the growth and metastasis of numerous tumors. Although both CD44 overexpression and loss have been implicated in tumor progression, the mechanism of CD44 down-regulation in these tumor types is not known. By immunoblot and reverse transcription-polymerase chain reaction analysis we determined that a cervical carcinoma cell line, C33A, lacks CD44 expression. To determine how CD44 is down-regulated in C33A cells, we utilized cell fusions of C33A cells with a CD44-expressing cell line (SAOS-2). We found that SAOS-2 fusion restored CD44 expression in C33A cells, suggesting that a trans-acting factor present in SAOS-2 cells promotes CD44 production. C33A cells are BRG-1-deficient, and we found that CD44 was absent in another BRG-1-deficient tumor cell line, indicating that loss of BRG-1 may be a general mechanism by which cells lose CD44. Reintroduction of BRG-1 into these cells restored CD44 expression. Furthermore, disruption of BRG-1 function through the use of dominant-negative BRG-1 demonstrated the requirement of BRG-1 in CD44 regulation. Finally, we show that Cyclin E overexpression resulted in the attenuation of CD44 stimulation, which is consistent with previous observations that Cyclin E can abrogate BRG-1 action. Taken together, these results suggest that BRG-1 is a critical regulator of CD44 expression, thus implicating SWI/SNF components in the regulation of cellular adhesion and metastasis.

Original languageEnglish (US)
Pages (from-to)9273-9278
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number12
DOIs
StatePublished - Mar 23 2001

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Strobeck, M. W., DeCristofaro, M. F., Banine, F., Weissman, B. E., Sherman, L. S., & Knudsen, E. S. (2001). The BRG-1 Subunit of the SWI/SNF Complex Regulates CD44 Expression. Journal of Biological Chemistry, 276(12), 9273-9278. https://doi.org/10.1074/jbc.M009747200