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Biochimie. 2014 Jan;96:22-7. doi: 10.1016/j.biochi.2013.08.021. Epub 2013 Sep 6.

n-3 polyunsaturated fatty acids and HER2-positive breast cancer: interest of the fat-1 transgenic mouse model over conventional dietary supplementation.

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  • 1Université de Bourgogne, UFR Sciences de la Vie, de la Terre et de l'Environnement, 6 Boulevard Gabriel, 21000 Dijon, France; INSERM UMR U866 Lipides Nutrition Cancer, Université de Bourgogne, 6 Boulevard Gabriel, 21000 Dijon, France.

Abstract

Overexpression of the tyrosine kinase receptor ErbB2/HER2/Neu, occurs in 25%-30% of invasive breast cancer (BC) with poor patient prognosis. Even if numerous studies have shown prevention of breast cancer by n-3 fatty acid intake, the experimental conditions under which n-3 fatty acids exert their protective effect have been variable from study to study, preventing unifying conclusions. Due to confounding factors, inconsistencies still remain regarding protective effects of n-3 polyunsaturated fatty acids (PUFA) on BC. When animals are fed with dietary supplementation in n-3 fatty acids (the traditional approach to modify tissue content and decrease the n-6/n-3 ratio) complex dietary interactions can occur among dietary lipids (antioxidants, vitamins…) that can modulate the activity of n-3 fatty acids. So, what are the specific roles of these n-3 PUFA in reducing breast cancer risk and particularly preventing HER2-positive breast cancer? In this review, we discuss crucial points that may account for discrepancies of results and provide a highly effective genetic approach that can eliminate confounding factors of diet for evaluating the molecular mechanisms of n-3 PUFA in HER2 signaling pathway regulation. The fat-1 transgenic mouse model is capable of converting n-6 to n-3 fatty acids leading to an increase in n-3 fatty acid content with a balanced n-6/n-3 fatty acid ratio in all tissues. The fat-1 mouse model allows well-controlled studies in HER2-positive breast cancer prevention to be performed, without the conflict of potential confounding factors of diet.

Copyright © 2013 Elsevier Masson SAS. All rights reserved.

KEYWORDS:

Fat-1 transgenic mouse model; HER2-positive breast cancer; n-3 fatty acids

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