Accession Number : ADA462337


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


Descriptive Note : Annual summary 1 Mar 2005-28 Feb 2006


Corporate Author : CALIFORNIA UNIV IRVINE


Personal Author(s) : Furuta, Saori


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a462337.pdf


Report Date : Mar 2006


Pagination or Media Count : 67


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.


Descriptors :   *MAMMARY GLANDS , *BREAST CANCER , *GENETIC DISEASES , EPITHELIUM , NEOPLASMS , GENES , CELLS(BIOLOGY) , PATHOGENESIS


Subject Categories : Genetic Engineering and Molecular Biology
      Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE