The inhibition of early stages of HER-2/neu-mediated mammary carcinogenesis by dietary n-3 PUFAs.

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. 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. 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.