Roles of Breast Cancer Susceptibility Genes BRCA's in Mammary Epithelial Cell Differentiation
Abstract
We examined if BRCA1 is involved in MEC differentiation and how its dysfunction pertains to breast tumor pathogenesis. We demonstrated that BRCA1 mediates acinar differentiation of MEC using 3-D culture. Reduction of BRCA1 by RNAi impairs acinus formation but enhances proliferation. Such aberrations can be rescued by expression of wild-type BRCA1 as well as a mutant in the central domain but not in the C-terminal BRCT domain, suggesting that the BRCT domain has a critical role in this process. Consistently, depletion of BRCA1 up-regulates the gene expression for proliferation but down-regulates that for differentiation. Moreover, application of the medium conditioned by differentiating normal MEC can reverse the phenotype of differentiation-defective breast cancer cells bearing reduced BRCA1 functions. This result implies BRCA1 is involved in secretion of certain paracrine/autocrine factors that induce MEC differentiation in response to extracellular matrix signals.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2006
- Accession Number
- ADA462337
Entities
People
- Saori Furuta
Organizations
- University of California, Irvine