Identification of a core member of the SWI/SNF complex, BAF155/SMARCC1, as a human tumor suppressor gene

Recent studies have established that two core members of the SWI/SNF chromatin remodeling complex, BRG1 and SNF5/INI1, possess tumor-uppressor activity in human and mouse cancers. While the third core member, BAF155, has been implicated by several studies as having a potential role in tumor development, direct evidence for its tumor suppressor activity has remained lacking. Therefore, we screened for BAF155 deficiency in a large number of human tumor cell lines. We identified two cell lines, the SNUC2B colon carcinoma and the SKOV3 ovarian carcinoma, displaying a complete loss of protein expression while maintaining normal levels of mRNA expression. The SKOV3 cell line possesses a heterozygous 4 bp deletion that results in an 855AA truncated protein, while the cause of the loss of BAF155 expression in the SNUC2B cell line appears due to a post-transcriptional error. However, the lack of detectable BAF155 expression did not affect sensitivity to RB-mediated cell cycle arrest. Re-expression of full length but not a truncated form of BAF155 in the two cancer cell lines leads to reduced colony forming ability characterized by replicative senescence but not apoptosis. Collectively, these data suggest that loss of BAF155 expression represents another mechanism for inactivation of SWI/SNF complex activity in the development in human cancer. Our results further indicate that the c-terminus proline-glutamine rich domain plays a critical role in the tumor suppressor activity of this protein.