More evidence that Omega 3s -
and Omega 6s (in excess -
) have a role in breast cancer risk reduction.
(Ooops just noted that Lani is quicker off the mark than me - thanks Lani - http://her2support.org/vbulletin/showthread.php?t=59076 )
FAT1 is a mouse with a gene from a worm inserted that allows them to convert Omega 6 to Omega 3; normally mammals including humans cannot convert Omega 6 to Omega 3, and we must get it from our diet, which is why getting Omega 3 in the diet is so important. Fat1 mice tend to change enough Omega 6 into Omega 3 to create an equal balance of the two in their body.
They compared how implanted HER2 cells grew in FAT1 and normal wild type (WT) mice.
Both mice were fed the same diet which contained lots of Omega 6 and very little Omega 3 (Safflower oil), but FAT1 mice (-: unlike the WT mice )-: could make their own Omega 3.
The implanted HER2 tumors initially grew in both normal (WT) and FAT1 mice, and continued to grow in the normal WT mice -, but in contrast shrunk and eventually disappeared - in the FAT1 mice.
The tumors in the FAT1 mice contained much more EPA and DHA and a much better Omega 3:6 ratio -.
Clearly we are not FAT1 mice, but nonetheless the results are intriguing.
(15-HEPE, 17-HDHA and PGE3 are downstream Omega 3 products produced in the body
https://www.caymanchem.com/app/templ.../catalog/14990
WT is the normal mouse (Wild Type)
http://www.ncbi.nlm.nih.gov/pubmed/24052576
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.
The full paper can be read free here (-: http://www.jlr.org/content/early/201...r.M042754.long and includes the comment below
"To test the hypothesis that balanced ratio of n-6/n-3 fatty acid is able to decrease the risk of
BC, we implanted E0771 mouse BC cells into the fat-1 and WT mice and examined the
tumorigenicity of inoculated tumor cells. As shown in Fig.1, there was a dramatic difference
in the tumor volume between fat-1 transgenic (n=10) and WT mice (n=6). Over an
observation period of 25 days, all mice initially developed a palpable tumor by day 7 but,
importantly, all the tumors in fat-1 mice never grew up more and all palpable tumors
disappeared at day 18. By contrast, all the tumors in wild-type mice continued to grow up
until host sacrifice. These findings clearly show that expression of fat-1 inhibits the growth of
BC cells in vivo and results in mammary tumor regression.
Inhibition"
"Tumor n-3 fatty acid enrichment and formation of PUFA-derived mediators
As shown in Fig. 3A, fatty acid composition of tumor total lipids revealed higher levels of
10
EPA (20:5n-3) and docosapentaenoic acid (DPA, 22:5n-3) in fat-1 transgenic mice compared
with WT animals, whereas AA (20:4n-6) was decreased by 70%. Interestingly, the n-6/n-3
PUFA ratio (Figure 3B) was significantly reduced in tumors from fat-1 mice (8.92±2.63)
compared to WT animals (30.51±6.99) despite the animals were fed the same diet. These
results indicate expression of fat-1 enriches the transgenic animals in n-3 PUFA at the
expense of n-6, giving a lower n-6/n-3 ratio."
The pictures of the dead mice and their tumors or lack of them are not pretty but exceptionally powerfully make the point of this important trial; and yes I do 'feel' for the mice. (page 27)
The graph of the relative tumor sizes is equally very powerful. (page 27)
All of which takes us back to a French paper in which it was noted that women with higher levels of DHA in breast tissue had a 70% lower risk of their excised breast tissue 'lumps' being cancerous