期刊
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
卷 46, 期 1, 页码 82-92出版社
ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
DOI: 10.1207/S15327914NC4601_11
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资金
- NATIONAL CANCER INSTITUTE [R01CA043894, P01CA072008, R01CA065579, P30CA023074] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P30ES006694] Funding Source: NIH RePORTER
- NCI NIH HHS [CA23074, CA43894, CA72008, CA65579] Funding Source: Medline
- NIEHS NIH HHS [ES-07091-22, ES06694] Funding Source: Medline
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 (10muM) but is strongly inhibited at higher cytotoxic concentrations (greater than or equal to100muM). Indication of phosphorylation of BRCA-1 by deoxycholate (100muM) at a lower dose was seen by Western blot analysis, whereas, at a higher dose, deoxycholate (200 and 300muM) 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.
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