Omega-3 Fatty Acids Delay The Growth Of Mammary Tumors In Mmtv-Erbb2 Mice

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Purpose: Dietary fats have long been suspected of contributing to breast cancer risk, but the effects of various fatty acids are still not clear. We used MMTV-Erbb2 transgenic mice to determine how different fatty acids influence mammary tumor development and what the possible mechanisms are. Methods and Results: Female MMTV-Erbb2 transgenic mice (FVB-Tg(MMTV-Erbb2)NK1Mul/J, n=13-14 per group) were placed on defined diets with 30% calories from fat, enriched in different types of fatty acids: saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), omega-3 polyunsaturated fatty acids (n-3 PUFA), omega-6 polyunsaturated fatty acids (n-6 PUFA) and control diet with a nutritionally balanced mixture of the above fatty acids. The results showed that the incidence of palpable mammary tumors, their multiplicity and average tumor weight were significantly lower in the n-3 PUFA enriched diet group than in other diet groups (p<0.05, ANOVA). Moreover, the tumors from the n-3 PUFA diet group showed decreased cell proliferation and increased apoptosis (as determined by immunohistochemical staining for Ki67 and cleaved caspase3, respectively) compared to other groups. However, there were no significant differences in the number of hyperplasic nodules detected in mammary glands by carmine alum whole mount staining. SFA, MUFA and n-6 PUFA were not statistically different from control. Conclusions: Our results suggest that n-3 PUFA can inhibit HER-2/neu-induced mammary tumor growth in this mouse model, but that n-3 PUFA has no effect on the very early stage of tumorigenesis. The mechanism of the antitumor effects of n-3 PUFA may be related to inhibition of cell proliferation and promotion of apoptosis. This project was supported by an Intramural Research Support Grant (Kulynych Fund) entitled: “Pilot study on the effects of different dietary fatty acids on mammary cancer risk”. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1828. doi:10.1158/1538-7445.AM2011-1828