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 BRGI 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 BRGI 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 BRGI 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 BRGI 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.