RNAi profiling of human MCF10A cells in 3-D culture for 15 h after treatment with BRCA1-RNAi vs Luc-RNAi adenovirus

ABSTRACT: BRCA1 exerts transcriptional repression through interaction with CtIP in the C-terminal BRCT domain and ZBRK1 in the central domain. A dozen of genes including angiopoietin-1 (ANG1), a secreted angiogenic factor, are co-repressed by BRCA1 and CtIP based on microarray analysis of mammary epithelial cells in 3-D culture. BRCA1, CtIP and ZBRK1 form a complex that coordinately represses ANG1 expression via a ZBRK1 recognition site in ANG1 promoter. Impairment of this complex upregulates ANG1, which stabilizes endothelial cells forming capillary-like network structure. Consistently, Brca1-deficient mouse mammary tumors exhibit accelerated growth, pronounced vascularization and overexpressed ANG1. These results suggest, besides its role in maintaining genomic stability, BRCA1 directly regulates

ORGANISM(S): Homo sapiens

SUBMITTER: Wen-Hwa Lee 

PROVIDER: E-GEOD-4750 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress