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A chemoprotective fish oil/pectin diet regulates the expression of the bcl‐2 oncogene by altering CpG island methylator phenotype (CIMP) in colon cancer
Author(s) -
Cho Youngmi,
Turner Nancy D.,
Davidson Laurie A.,
Chapkin Robert S.,
Lupton Joanne R.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.977.7
Subject(s) - azoxymethane , methylation , dna methylation , apoptosis , biology , oncogene , microbiology and biotechnology , bisulfite , cancer research , cpg site , dna glycosylase , epigenetics , colorectal cancer , fish oil , cancer , gene expression , dna , dna damage , biochemistry , gene , fish <actinopterygii> , genetics , cell cycle , fishery
We have demonstrated that diets containing fish oil and pectin (FO/P) reduce colon tumor incidence relative to those containing corn oil and cellulose (CO/C) in part by inducing apoptosis. CO/C, as compared to FO/P, promotes colonocyte expression of the anti‐apoptotic protein, bcl‐2, and bcl‐2 promoter methylation is altered in colon cancer. To determine if CO/C promotes bcl‐2 expression by reducing promoter methylation in colon cancer, we examined bcl‐2 promoter methylation and mRNA levels, and colonocyte apoptosis (TUNEL assay). Rats were provided diets containing FO/P or CO/C, and were terminated 36 wk after azoxymethane injection (2×, 15 mg/kg BW, sc). DNA isolated from 10 μm sections of PFA‐fixed colon carcinomas was bisulfite modified and amplified by real time qPCR to assess regions of the bcl‐2 CpG islands. Scraped mucosa from the same rats was also used to quantify bcl‐2 mRNA levels. FO/P treatment increased bcl‐2 DNA methylation (p = 0.055) and apoptosis (p = 0.022) as compared to CO/C. Data analysis revealed a negative relationship between bcl‐2 DNA methylation and bcl‐2 mRNA levels. We conclude that dietary FO/P promotes apoptosis by enhancing bcl‐2 promoter methylation relative to a CO/C diet. This study is the first to detect a diet effect on promoter methylation of the bcl‐2 oncogene in the colon. Funded by NSBRI NASA NCC 9‐58 and NIH CA59034.