The BRG1- and hBRM-Associated Factor BAF57 Induces Apoptosis by Stimulating Expression of the Cylindromatosis Tumor Suppressor Gene

Authors:
Wang L, Baiocchi RA, Pal S, Mosialos G, Caligiuri M and Sif S
In:
Source: Mol Cell Biol
Publication Date: (2005)
Issue: 25(18): 7953-7965
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
MCF7
Species: human
Tissue Origin: breast
BT549
Species: human
Tissue Origin: breast
MCF7 tet
Species: human
Tissue Origin: breast
Epithelial, mammary, human (HMEC)
Species: human
Tissue Origin: breast
HCC1937
Species: human
Tissue Origin: breast
Platform:
Nucleofectorâ„¢ I/II/2b
Abstract
Mutation of BRG1, hBRM, and their associated factors, INI1 and BAF57, in primary human tumors has suggested that inactivation of human SWI/SNF (hSWI/SNF) complexes may be involved in neoplastic transformation. BT549 is an invasive human breast carcinoma cell line that lacks expression of BAF57, a key hSWI/SNF subunit that mediates interaction with transcriptional activators and corepressors. In this study we investigated the role of BAF57 in suppressing tumorigenesis by establishing BT549 stable cell lines that expresses full-length BAF57 protein. BT549 clones expressing BAF57 demonstrated marked phenotypic changes, slow growth kinetics, and restoration of contact inhibition. Altered growth was found to be due in part to cell cycle arrest and induction of apoptosis. Furthermore, microarray analysis revealed that BAF57-mediated cell death was associated with up-regulation of proapoptotic genes including the tumor suppressor familial cylindromatosis (CYLD), which was found to be a direct target of BAF57 as determined by chromatin immunoprecipitation analysis. Increased expression of CYLD in BT549 cells induced apoptosis, while its suppression by small interfering RNA inhibited cell death in BAF57 expressing BT549 cells. These findings demonstrate the importance of BAF57 in cell growth regulation and provide a novel link between hSWI/SNF chromatin remodelers and apoptosis.