BAF180 is a critical regulator of p21 induction and a tumor suppressor mutated in breast cancer

Authors:
Xia W, Nagase S, Montia AG, Kalachikov SM, Keniry M, Su T, Memeo L, Hibshoosh H, Parsons R
In:
Source: Cancer Res
Publication Date: (2008)
Issue: 68(6): 1667-74
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
MCF10A
Species: human
Tissue Origin: breast
Platform:
Nucleofector® I/II/2b
Abstract
Screening for tumor suppressor genes in breast cancer revealed multiple truncating mutations of PB1, which encodes the BAF180 subunit of the PBAF chromatin remodeling complex. Mutation was associated with loss of heterozygosity of the wild-type allele. BAF180 complementation of BAF180-mutant tumor cells caused G(1) arrest that was dependent on increased expression of the cyclin/cyclin-dependent kinase inhibitor p21/WAF1/CIP1. Endogenous wild-type BAF180 bound to the p21 promoter and was required for proper p21 expression and G(1) arrest after transforming growth factor-beta and gamma-radiation treatment. BAF180 thus functions on two tumor suppressor signaling pathways as a physiologic mediator of p21 expression. We conclude that BAF180 suppresses tumorigenesis, at least in part, through its ability to regulate p21.