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 Romagnolo, Ryan B. Chirnomas, Jennifer Ku, Brandon D. Jeffy, Claire M. Payne, Hana Holubec, Lois Ramsey, Harris Bernstein, Carol Bernstein, Kathleen Kunke, Achyut K Bhattacharyya, James A 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
Publication statusPublished - 2003

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ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Oncology
  • Food Science

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