Concomitant down-regulation of BRM and BRG1 in human tumor cell lines: differential effects on RB-mediated growth arrest vs CD44 expression.
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.
Reisman
David N
DN
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295, USA.
Strobeck
Matthew W
MW
Betz
Bryan L
BL
Sciariotta
Janiece
J
Funkhouser
William
W
Murchardt
Christian
C
Yaniv
Moshe
M
Sherman
Larry S
LS
Knudsen
Erik S
ES
Weissman
Bernard E
BE
D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle; D019925:Cyclin A / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004265:DNA Helicases; D015536:Down-Regulation; D029721:Drosophila Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D016160:Retinoblastoma Protein / Q000378:metabolism*; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D019925:Cyclin A; D029721:Drosophila Proteins; D018960:Hyaluronan Receptors; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D016160:Retinoblastoma Protein; D017412:Ribonucleoprotein, U1 Small Nuclear; C084011:SMARCA2 protein, human; C499503:Smarca2 protein, mouse; D014157:Transcription Factors; C089969:snf protein, Drosophila; D004247:DNA; C084108:SMARCA4 protein, human; C513194:Smarca4 protein, mouse; D004265:DNA Helicases