Deoxycholate, an endogenous tumor promoter and DNA damaging agent, modulates BRCA-1 expression in apoptosis-sensitive epithelial cells: loss of BRCA-1 expression in colonic adenocarcinomas

Nutr Cancer. 2003;46(1):82-92. doi: 10.1207/S15327914NC4601_11.


Deoxycholate, a bile salt present at high levels in the colonic lumen of individuals on a high-fat diet, is a promoter of colon cancer. Deoxycholate also causes DNA damage. BRCA-1 functions in repair of DNA and in induction of apoptosis. We show that, when cultured cells of colonic origin are exposed to deoxycholate at different concentrations, BRCA-1 expression is induced at a low noncytotoxic concentration (10 microM) but is strongly inhibited at higher cytotoxic concentrations ( > or =100 microM). Indication of phosphorylation of BRCA-1 by deoxycholate (100 microM) at a lower dose was seen by Western blot analysis, whereas, at a higher dose, deoxycholate (200 and 300 microM) caused a complete loss of BRCA-1 expression. We show that BRCA-1 is substantially lower in colon adenocarcinomas from five patients compared with associated non-neoplastic colon tissue from the same patients, suggesting that the loss of BRCA-1 expression contributes to the malignant phenotype. In the non-neoplastic colon tissue, BRCA-1 was localized to the nongoblet cells. Our results imply that reduced expression of BRCA-1 may be associated with carcinoma of the colon.

Publication types

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

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Apoptosis / drug effects*
  • Blotting, Western
  • Carcinogens / pharmacology
  • Cell Survival / drug effects
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • DNA Damage*
  • Deoxycholic Acid / pharmacology*
  • Detergents / pharmacology
  • Epithelial Cells / drug effects
  • Epithelial Cells / pathology
  • Gene Expression / drug effects*
  • Genes, BRCA1 / drug effects*
  • Humans
  • Middle Aged
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured


  • Carcinogens
  • Detergents
  • Deoxycholic Acid