Wild-type BRCA1, but not mutated BRCA1, regulates the expression of the nuclear form of beta-catenin

Mol Cancer Res. 2010 Mar;8(3):407-20. doi: 10.1158/1541-7786.MCR-09-0403. Epub 2010 Mar 9.


BRCA1 is an essential caretaker protein in the surveillance of DNA damage, is mutated in approximately 50% of all hereditary breast cancer cases, and its expression is frequently decreased in sporadic breast cancer. beta-Catenin is a multifunctional protein that forms adhesion complex with E-cadherins, alpha-catenin, and actin, and plays a central role in Wnt signaling through its nuclear translocation and activation of beta-catenin-responsive genes. Although significant progress has been made in understanding the Wnt/beta-catenin and BRCA1 signaling cascades, it is not known whether there is a link between beta-catenin and BRCA1. We observed that the expression of the active nuclear form of beta-catenin (also known as ABC, Ser37/Thr41-nonphosphorylated beta-catenin, dephosphorylated beta-catenin) was lower or absent in the nucleus in most BRCA1 familial breast cancer tissues (17 cases) compared with sporadic breast cancer (14 samples) and normal breast tissues. Wild-type-BRCA1, but not mutated BRCA1, interacted with beta-catenin and increased the levels of beta-catenin protein expression in vitro. Furthermore, H(2)O(2) induced the interaction of the nuclear form of beta-catenin with BRCA1. The active form of beta-catenin protein was downregulated upon exposure to H(2)O(2) in the nucleus of BRCA1-deficient HCC1937 breast cancer cells, whereas reconstitution of WT-BRCA1 in HCC1937 cells inhibited this downregulation. This study provides evidence of a novel interaction between BRCA1 and beta-catenin, and that loss of BRCA1 leads to impaired expression of the nuclear form of beta-catenin, which may contribute to the pathogenesis of breast cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • BRCA1 Protein / genetics*
  • BRCA1 Protein / metabolism
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Cell Line, Tumor
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Mutation / genetics
  • Oxidants / pharmacology
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics
  • Signal Transduction / genetics
  • beta Catenin / genetics
  • beta Catenin / metabolism*


  • BRCA1 Protein
  • BRCA1 protein, human
  • Oxidants
  • beta Catenin
  • Hydrogen Peroxide