Although recent research suggests a link between the ratio of omega-6 (n-6) to omega-3 (n-3] fatty acids and cancer risk, the question as to whether a high n-6/n-3 ratio (>15), as found in most Western people, promotes tumorigenesis or if a balanced n-6/n-3 fatty acid ratio can reduce cancer development remains to be clarified in well-qualified experimental animal models. My lab has recently generated a novel transgenic mouse model that expresses the C. elegans fat-1 gene capable of converting n-6 to n-3 fatty acids, which is absent in wild type mice. These transgenic animals are characterized by an abundance of n-3 fatty acids and a balanced n-6/n-3 fatty acid ratio (1:1) in their tissues and organs, whereas wild type mice have a ratio of > 30 when maintained on the same diet high in n-6 and deficient in n-3 fatty acids. Use of these transgenic animals can avoid potential confounding factors of diet and will provide more reliable evidence on the effects of n-3 fatty acids and n-6/n-3 ratio. Our pilot experiments showed a marked difference in tumor formation and growth of B16 melanoma between wild type and fat-1 transgenic mice. This exciting observation led us to hypothesize that a balanced n-6/n-3 fatty acid ratio may have a protective effect against cancer development, and that this anticancer effect is induced by changes in cancer-related gene expression mediated by certain eicosanoids or lipid mediators.
Specific aims are: 1) To determine the tumorigenicity and metastasis of B16 melanoma cells implanted in the fat-1 transgenic and wild type mice; 2) To characterize gene expression patterns of the tumor cells and stromal tissues in the fat-1 transgenic and wild type mice using a microarray technology; and 3) To determine if changes in eicosanoid biosynthesis are responsible for the effects on gene expression and tumor growth. Several approaches including microarray and lipidomics will be used to identify the involved mediators. Information derived from these studies will increase our understanding of the importance of n-3 fatty acids as well as n-6/n-3 fatty acid ratio in cancer prevention and help guide dietary advice. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA113605-03
Application #
7426822
Study Section
Chemo/Dietary Prevention Study Section (CDP)
Program Officer
Perloff, Marjorie
Project Start
2006-07-01
Project End
2010-05-31
Budget Start
2008-06-01
Budget End
2009-05-31
Support Year
3
Fiscal Year
2008
Total Cost
$241,294
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
He, Chengwei; Qu, Xiying; Wan, Jianbo et al. (2012) Inhibiting delta-6 desaturase activity suppresses tumor growth in mice. PLoS One 7:e47567
Kang, Jing X (2011) The omega-6/omega-3 fatty acid ratio in chronic diseases: animal models and molecular aspects. World Rev Nutr Diet 102:22-9
Kang, Jing X (2011) Omega-3: a link between global climate change and human health. Biotechnol Adv 29:388-90
White, Phillip J; Arita, Makoto; Taguchi, Ryo et al. (2010) Transgenic restoration of long-chain n-3 fatty acids in insulin target tissues improves resolution capacity and alleviates obesity-linked inflammation and insulin resistance in high-fat-fed mice. Diabetes 59:3066-73
Shen, Li Rong; Lai, Chao Qiang; Feng, Xiang et al. (2010) Drosophila lacks C20 and C22 PUFAs. J Lipid Res 51:2985-92
Griffitts, J; Saunders, D; Tesiram, Y A et al. (2010) Non-mammalian fat-1 gene prevents neoplasia when introduced to a mouse hepatocarcinogenesis model: Omega-3 fatty acids prevent liver neoplasia. Biochim Biophys Acta 1801:1133-44
Mayer, Konstantin; Kiessling, Almuth; Ott, Juliane et al. (2009) Acute lung injury is reduced in fat-1 mice endogenously synthesizing n-3 fatty acids. Am J Respir Crit Care Med 179:474-83
He, Chengwei; Qu, Xiying; Cui, Libin et al. (2009) Improved spatial learning performance of fat-1 mice is associated with enhanced neurogenesis and neuritogenesis by docosahexaenoic acid. Proc Natl Acad Sci U S A 106:11370-5
Liu, Jing; He, Chengwei; Zhou, Keyuan et al. (2009) Coptis extracts enhance the anticancer effect of estrogen receptor antagonists on human breast cancer cells. Biochem Biophys Res Commun 378:174-8
Freudiger, Christian W; Min, Wei; Saar, Brian G et al. (2008) Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy. Science 322:1857-61

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