title: Identification of a core member of the SWI/SNF complex, BAF155/SMARCC1, as a human tumor suppressor gene.
abstract: Recent studies have established that two core members of the SWI/SNF chromatin remodeling complex, BRG1 and SNF5/INI1, possess tumor-suppressor 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 2 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 4bp 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: DelBove
authors.forename: Gary
authors.initials: G
authors.lastname: Rosson
authors.forename: Matthew
authors.initials: M
authors.lastname: Strobeck
authors.forename: Jianguang
authors.initials: J
authors.lastname: Chen
authors.forename: Trevor K
authors.initials: TK
authors.lastname: Archer
authors.forename: Weidong
authors.initials: W
authors.lastname: Wang
authors.forename: Erik S
authors.initials: ES
authors.lastname: Knudsen
authors.forename: Bernard E
authors.initials: BE
authors.lastname: Weissman
mesh_terms: D000375:Aging / Q000235:genetics; D000595:Amino Acid Sequence; D017209:Apoptosis; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics* / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D050505:Mutant Proteins; D012333:RNA, Messenger; C101681:SMARCC1 protein, human; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors