Document Detail

The inhibition of early stages of HER-2/neu-mediated mammary carcinogenesis by dietary n-3 PUFAs.
MedLine Citation:
PMID:  23213007     Owner:  NLM     Status:  MEDLINE    
SCOPE: We previously demonstrated that lifelong feeding of diets enriched in n-3 fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) significantly inhibits HER-2/neu-mediated mammary tumorigenesis in mice. Of interest is whether dietary n-3 fatty acids exert effects at early stages of mammary carcinogenesis.
METHODS AND RESULTS: Seven-week-old female MMTV-HER-2/neu transgenic mice were randomized to AIN-based semipurified diets containing either fish or corn oil at 25% energy. Mice were evaluated at 25, 30, and 35 weeks with analysis of mammary glands for atypical ductal hyperplasia (hematoxylin and eosin), cell proliferation (Ki67 immunostaining), and fatty acid synthase and cyclooxygenase-2 gene expression (qRT-PCR). Tissue fatty acid profiles were quantitated by GC. Atypia grade decreased significantly in mice fed fish oil (p = 0.002). Mammary epithelial cells in mammary glands from mice fed fish oil also had an eightfold lower percentage of Ki67 expression. COX-2 expression in mammary fat-pads significantly decreased in mice fed fish versus corn oil enriched diets.
CONCLUSION: Dietary fish oil inhibits atypical ductal hyperplasia at early stages of HER-2/neu-mediated mammary carcinogenesis relative to corn oil diets. This histologic change is associated with suppression of mammary epithelial cell proliferation and decreased COX-2 expression in mammary tissue.
Lisa D Yee; Deepak Agarwal; Thomas J Rosol; Amy Lehman; Min Tian; Jennifer Hatton; Jessica Heestand; Martha A Belury; Steven K Clinton
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-12-05
Journal Detail:
Title:  Molecular nutrition & food research     Volume:  57     ISSN:  1613-4133     ISO Abbreviation:  Mol Nutr Food Res     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-23     Completed Date:  2013-07-11     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  101231818     Medline TA:  Mol Nutr Food Res     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  320-7     Citation Subset:  IM    
Copyright Information:
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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MeSH Terms
Cell Proliferation / drug effects
Corn Oil / administration & dosage
Cyclooxygenase 2 / genetics,  metabolism
Disease Models, Animal
Docosahexaenoic Acids / pharmacology*
Eicosapentaenoic Acid / pharmacology*
Fatty Acid Synthases / genetics,  metabolism
Fish Oils / administration & dosage
Gene Expression Regulation
Mammary Neoplasms, Animal / diet therapy*
Mammary Tumor Virus, Mouse
Mice, Transgenic
Receptor, erbB-2 / antagonists & inhibitors,  genetics*,  metabolism
Grant Support
P30 CA016058/CA/NCI NIH HHS; R21 CA116024/CA/NCI NIH HHS; R21 CA116024/CA/NCI NIH HHS
Reg. No./Substance:
0/Fish Oils; 25167-62-8/Docosahexaenoic Acids; 8001-30-7/Corn Oil; AAN7QOV9EA/Eicosapentaenoic Acid; EC 1.14.99.-/Ptgs2 protein, mouse; EC 2; EC Acid Synthases; EC protein, mouse; EC, erbB-2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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