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Identification of a Molecular Signature Underlying Inhibition of Mammary Carcinoma Growth by Dietary N-3 Fatty Acids.
MedLine Citation:
PMID:  22651929     Owner:  NLM     Status:  Publisher    
An increased ratio of dietary n-3 relative to n-6 fatty acids has been shown to inhibit the development of mammary cancer in animal models. However, the molecular mechanisms by which n-3 fatty acids affect tumor growth remain unknown. Here, we investigated the effects of varying dietary ratios of n-3:n-6 fatty acids on cell signaling in a rat model of chemically-induced mammary carcinoma. Cell proliferation was reduced by 60% in carcinomas from the high n-3:n-6 treatment group compared with the low treatment and control groups. These changes were associated with decreased cyclin D1 and phospho-retinoblastoma protein expression and increased levels of cyclin dependent kinase inhibitors, CIP1(p21), and KIP1 (p27). In addition, the apoptotic index was increased in carcinomas from the high n-3:n-6 group and was associated with elevated apoptotic protease activating factor 1 (APAF-1) and a higher ratio of Bax/Bcl-2. Interestingly, changes in protein expression were consistent with reduced inflammation and suppressed mTOR activity, and the molecular signature associated with high n-3:n-6 treatment revealed changes in peroxisome proliferator-activated receptor-γ activation and suppression of lipid synthesis. Together, our findings indicate that the molecular effects of high dietary n-3 to n-6 ratios are heterogeneous in nature, but point to consistent changes in lipid metabolism pathways, which may serve as potential therapeutic targets for cancer prevention and control. This study identifies the pathways modulated by dietary fatty acid ratios in a rat model of breast cancer, with implications for cancer prevention.
Weiqin Jiang; Zongjian Zhu; John N McGinley; Karam El-Bayoumy; Andrea Manni; Henry J Thompson
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-31
Journal Detail:
Title:  Cancer research     Volume:  -     ISSN:  1538-7445     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-6-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Cancer Prevention Laboratory, Colorado State University.
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