The BRG-1 subunit of the SWI/SNF complex regulates CD44 expression.
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.
Strobeck
M W
MW
Department of Cell Biology, University of Cincinnati College of Medicine, Vontz Center for Molecular Studies, Cincinnati, Ohio 45267-0521, USA.
DeCristofaro
M F
MF
Banine
F
F
Weissman
B E
BE
Sherman
L S
LS
Knudsen
E S
ES
D001483:Base Sequence; D019927:Cyclin E / Q000378:metabolism; D004265:DNA Helicases; D017931:DNA Primers; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007150:Immunohistochemistry; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D019927:Cyclin E; D017931:DNA Primers; D018960:Hyaluronan Receptors; D009687:Nuclear Proteins; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases