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

Donato F. Romagnolo, Ryan B. Chirnomas, Jennifer Ku, Brandon D. Jeffy, Claire M. Payne, Hana Holubec, Lois Ramsey, Harris Bernstein, Carol Bernstein, Kathleen Kunke, Achyut Bhattacharyya, James Warneke, Harinder Garewal

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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 μM) but is strongly inhibited at higher cytotoxic concentrations (≥ 100 μM). Indication of phosphorylation of BRCA-1 by deoxycholate (100 μM) at a lower dose was seen by Western blot analysis, whereas, at a higher dose, deoxycholate (200 and 300 μM) 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.

Original languageEnglish (US)
Pages (from-to)82-92
Number of pages11
JournalNutrition and cancer
Volume46
Issue number1
DOIs
StatePublished - Jan 1 2003

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ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Oncology
  • Nutrition and Dietetics
  • Cancer Research

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