PREVENTION OF HER2+ breast cancer may lie in n-3 Polyunsaturated fatty acids
J Lipid Res. 2013 Sep 19. [Epub ahead of print]
Inhibition of the HER2 pathway by n-3 polyunsaturated fatty acids prevents breast cancer in fat-1 transgenic mice.
Zou Z, Bellenger S, Massey KA, Nicolaou A, Geissler A, Bidu C, Bonnotte B, Pierre AS, Minville-Walz M, Rialland M, Seubert J, Kang JX, Lagrost L, Narce M, Bellenger J.
Source
Universite de Bourgogne, France;
Abstract
Overexpression of the tyrosine kinase receptor ErbB2/HER2/Neu, occurs in 25% to 30% of invasive breast cancer (BC) with poor patient prognosis. Due to confounding factors, inconsistencies still remain regarding protective effects of n-3 polyunsaturated fatty acids (PUFA) on BC. We therefore evaluated whether fat-1 transgenic mice, endogenously synthesizing n-3 PUFA from n-6 PUFA, were protected against BC development and we then aimed to study in vivo a mechanism potentially involved in such protection. E0771 BC cells were implanted into fat-1 and wild-type (WT) mice. After tumorigenesis examination, we analyzed the expression of proteins involved in HER2 signaling pathway and lipidomic analyses were performed in tumor tissues and plasma. Our results showed that tumors totally disappeared by day 15 in fat-1 mice when they continued to grow up in the WT. This prevention can be related in part to significant repression of the HER2/beta-catenin signaling pathway and formation of significant levels of n-3 PUFAs derived bioactive mediators (particularly 15-HEPE, 17-HDHA and PGE3) in the tumor of fat-1 mice compared to WT. All together these data demonstrate an anti-BC effect of n-3 PUFAs through, at least in part, HER2 signaling pathway downregulation, and highlight the importance of gene-diet interactions in BC.
KEYWORDS:
Breast cancer, Cancer, Eicosanoids, HER2 signaling pathway, Mammary gland, Omega-3 fatty acids, PUFA-derived mediators, Prostaglandins, fat-1 mice, n-3 PUFA
PMID: 24052576
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