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The inhibition of early stages of HER ‐2/neu‐mediated mammary carcinogenesis by dietary n ‐3 PUFA s
Author(s) -
Yee Lisa D.,
Agarwal Deepak,
Rosol Thomas J.,
Lehman Amy,
Tian Min,
Hatton Jennifer,
Heestand Jessica,
Belury Martha A.,
Clinton Steven K.
Publication year - 2013
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201200445
Subject(s) - eicosapentaenoic acid , fish oil , docosahexaenoic acid , mammary gland , biology , corn oil , endocrinology , medicine , mammary tumor , polyunsaturated fatty acid , carcinogenesis , hyperplasia , fatty acid , biochemistry , cancer , breast cancer , fishery , fish <actinopterygii>
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 ( K i67 immunostaining), and fatty acid synthase and cyclooxygenase‐2 gene expression (q RT ‐ 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 K i67 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.