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Open Access Research

Mammary tumour development is dose-dependently inhibited by n-3 polyunsaturated fatty acids in the MMTV-neu(ndl)-YD5 transgenic mouse model

Michael A Leslie1, Salma A Abdelmagid1, Kate Perez1, William J Muller2 and David WL Ma1*

Author Affiliations

1 Department of Human Health and Nutritional Sciences, University of Guelph, Animal Science/Nutrition Building, Room 342, 491 Gordon Street, N1G 2W1 Guelph, ON, Canada

2 Molecular Oncology Labs, McGill University, Royal Victoria Hospital, Montreal, QC, Canada

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Lipids in Health and Disease 2014, 13:96  doi:10.1186/1476-511X-13-96

Published: 11 June 2014

Abstract

Background

Breast cancer is attributable to modifiable risk factors including the intake of dietary n-3 polyunsaturated fatty acids (PUFA). A key piece of evidence, yet to be addressed, that would demonstrate a causal relationship between n-3 PUFA and breast cancer, is a dose-dependent effect of n-3 PUFA on tumour outcomes. Thus, the objective of the present study was to determine whether n-3 PUFA reduces mammary gland tumor outcomes in a dose-dependent manner in female MMTV-neu(ndl)-YD5 transgenic mice, an aggressive model of human breast cancer.

Methods

Harems were provided one of three experimental diets comprised of 0, 3 or 9% (w/w) menhaden fish oil containing n-3 PUFA. Female offspring were weaned onto the same parental diet and maintained on their respective diet for 20 weeks. Tumour onset, size and multiplicity were measured throughout the study. Fatty acid composition of mammary gland and tumours were determined by gas–liquid chromatography.

Results

Tumour size was significantly (p < 0.05) reduced in a dose-dependent manner. n-3 PUFA were also incorporated in a dose-dependent manner; differential incorporation was observed for eicosapentaenoic and docosapentaenoic acids into mammary gland tissue, while docosahexaenoic acid was preferentially incorporated into tumours.

Conclusion

Overall, the present study provides fundamental knowledge about the dose-dependent effect of n-3 PUFA on tumour outcomes in a pre-clinical model and also sheds light on the differential role of individual n-3 PUFA on tumour outcomes.

Keywords:
n-3 PUFA; Eicosapentaenoic acid; Docosahexaenoic acid; Mammary gland; MMTV-neu mice; Breast cancer; Tumour; Tumour multiplicity; Tumour volume; Phospholipids