Roles of Breast Cancer Susceptibility Genes BRCA's in Mammary Epithelial Cell Differentiation

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 ANG1expression 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 the expression of angiogenic factors to modulate the tumor microenvironment.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Mar 01, 2007
Accession Number
ADA469943

Entities

People

  • Saori Furuta

Organizations

  • University of California, Irvine

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Blood
  • Blood Vessels
  • Breast Cancer
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Culture Techniques
  • Endothelial Cells
  • Epithelial Cells
  • Growth Factors
  • Medical Personnel
  • Microarray Analysis
  • Microvessels
  • Neoplasms
  • Proteins
  • Three Dimensional

Fields of Study

  • Biology
  • Chemistry

Readers

  • Molecular Biology and Genetics
  • Molecular and genetic basis of cancer.