RAS TRANSFORMATION IS ASSOCIATED WITH DECREASED EXPRESSION OF THE BRMSNF2-ALPHA ATPASE FROM THE MAMMALIAN SWI-SNF COMPLEX/

The brm and BRG-1 proteins are mutually exclusive subunits of the mamm alian SWI-SNF complex. Within this complex, they provide the ATPase ac tivity necessary for transcriptional regulation by nucleosome disrupti on. Both proteins were recently found to interact with the p105Rb tumo r suppressor gene product, suggesting a role for the mammalian SWI-SNF complex in the control of cell growth. We show here that the expressi on of brm, but not BRG-1, is negatively regulated by mitogenic stimula tion, and that growth arrest of mouse fibroblasts leads to increased a ccumulation of the brm protein, The expression of this protein is also down-regulated upon transformation by the ras oncogene. Re-introducti on of brm into ras transformed cells leads to partial reversion of the transformed phenotype by a mechanism that depends on the ATPase domai n of the protein. Our data suggest that increased levels of brm protei n favour the withdrawal of the cell from the cycle whereas decreased e xpression of the brm gene may facilitate cellular transformation by va rious oncogenes.