Abstract
In this study, we determined the phospholipid FA composition in the mammary gland of the transgenic Fat-1 mouse. This is the first animal model developed that can endogenously synthesize n−3 PUFA. The synthesis of n−3 PUFA is achieved through the expression of the fat-1 transgene encoding for an n−3 desaturase from Caenorhabditis elegans, which utilizes n−6 PUFA as substrate. Wild-type and Fat-1 female mice were terminated at 7 wk of age and the fifth mammary gland was removed. Lipids were extracted and phospholipids were separated by TLC and converted to FAME for analysis by GC. There was no significant change in total saturated, monounsaturated, and PUFA composition. However, there was a significant increase in total n−3 PUFA and a corresponding decrease in n−6 PUFA. The major n−3 PUFA that were enriched included 20:5n−3 and 22:6n−3. The n−6 PUFA that were reduced included 20:4n−6, 22:4n−6, and 22:5n−6. Overall, these findings demonstrate that female Fat-1 mice have elevated levels of n−3 PUFA in the mammary gland. Moreover, the n−3 desaturase products are the same n−3 PUFA found in fish oil, which have been shown to have chemoprotective properties against breast cancer. Therefore, this newly developed mouse model may be highly useful for investigating molecular and cellular mechanisms by which n−3 PUFA prevents and inhibits breast cancer growth.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Terry, P.D., Rohan, T.E., and Wolk, A. (2003) Intakes of Fish and Marine Fatty Acids and the Risks of Cancers of the Breast and Prostate and of Other Hormone-Related Cancers: A Review of the Epidemiologic Evidence. Am. J. Clin. Nutr. 77, 532–543.
Willett, W.C. (1999) Dietary Fat and Breast Cancer, Toxicol. Sci. 52 (Suppl.), 127–146.
Baracos, V.E., mazurak, V.C., and Ma, D.W.L. (2004) n−3 Polyunsaturated Fatty Acids Throughout the Cancer Trajectory: Influence on Disease Incidence, Progression, Response to Therapy and Cancer-Associated Cachexia, Nutr. Res. Rev. 17, 177–192.
Gago-Dominguez, M., Yuan, J.M., Sun, C.L., Lee, H.P., and Yu, M.C. (2003) Opposing Effects of Dietary n−3 and n−6 Fatty Acids on Mammary Carcinogenesis: The Singapore Chinese Health Study, Br. J. Cancer 89, 1686–1692.
Connolly, J.M., Gilhooly, E.M., and Rose, D.P. (1999) Effects of Reduced Dietary Linoleic Acid Intake, Alone or Combined with an Algal Source of Docosahe xaenoic Acid, on MDA-MB-231 Breast Cancer Cell Growth and Apoptosis in Nude Mice, Nutr. Cancer 35, 44–49.
Hamid, R., Singh, J., Reddy, B.S., and Cohen, L.A. (1999) Inhibition by Dietary Menhaden Oil of Cyclooxygenase-1 and-2 in N-Nitrosomethylurea-Induced Rat Mammary Tumors, Int. J. Oncol. 14, 523–528.
Hardman, W.E., Avula, C.P., Fernandes, G., and Cameron, I.L. (2001) Three Percent Dietary Fish Oil Concentrate Increased Efficacy of Doxorubicin Against MDA-MB 231 Breast Cancer Xenografts, Clin. Cancer Res. 7, 2041–2049.
Rose, D.P., Connolly, J.M., Rayburn, J., and Coleman, M. (1995) Influence of Diets Containing Eicosapentaenoic or Docosahex aenoic Acid on Growth and Metastasis of Breast Cancer Cells in Nude Mice, J. Natl. Cancer Inst. 87, 587–592.
Thoennes, S.R., Tate, P.L., Price, T.M., and Kilgore, M.W. (2000) Differential Transcriptional Activation of Peroxisome Prolife rator-Activated Receptor γ by Omega-3 and Omega-6 Fatty Acids in MCF-7 Cells. Mol. Cell. Endocrinol. 160, 67–73.
Rose, D.P. (1997) Dietary Fat. Fatty Acids and Breast Cancer, Breast Cancer 4, 7–16.
Albino, A.P., Juan, G., Traganos, F., Reinhart, L., Connolly, J., Rose, D.P., and Darzynkiewicz, Z. (2000) Cell Cycle Arrest and Apoptosis of Melanoma Cells by Docosahexaenoic Acid: Association with Decreased pRb Phosphorylation. Cancer Res. 60, 4139–4145.
Burgermeister, E., Tencer, L., and Liscovitch, M. (2003) Peroxisome Proliferator-Activated Receptor-γ Upregulates Cave olin-1 and Caveolin-2 Expression in Human Carcinoma Cells, Oncogene 22, 3888–3900.
Jump, D.B. (2004) Fatty Acid Regulation of Gene Transcription, Crit. Rev. Clin. Lab. Sci. 41, 41–78.
Larsson, S.C., Kumlin, M., Ingelman-Sundberg, M., and Wolk, A. (2004) Dietary Long-Chain n−3 Fatty Acids for the Prevention of Cancer: A Review of Potential Mechanisms. Am. J. Clin. Nutr. 79, 935–945.
Ma, D.W., Seo, J., Davidson, L.A., Callaway, E.S., Fan, Y.Y., Lupton, J.R., and Chapkin, R.S. (2004) n−3 PUFA Alter Caveolae Lipid Composition and Resident Protein Localization in Mouse Colon. FASEB J. 18, 1040–1042.
Ma, D.W.L., Seo, J., Switzer, K.C., Fan, Y.Y., McMurray, D.N., Lupton, J.R., and Chapkin, R.S. (2004) n−3 PUFA and Membrane Microdomains: A New Frontier in Bioactive Lipid Research, J. Nutr. Biochem., 15, 700–706.
Kang, J.X., Wang, J., Wu, L., and Kang, Z.B. (2004) Transgenic Mice: Fat-1 Mice Convert n−6 to n−3 Fatty Acids. Nature 427, 504.
Folch, J., Lees, M., and Sloane Stanley, G.H. (1957) A Simple Method for the Isolation and Purification of Total Lipides from Animal Tissues. J. Biol. Chem. 226, 497–509.
Touchstone, J.C., Chen, J.C., and Beaver, K.M. (1980) Improved Separation of Phospholipids in Thin Layer Chromatography, Lipids 15, 61–62.
Ge, Y., Chen, Z., Kang, Z.B., Cluette-Brown, J., Laposata, M., and Kang, J.X. (2002) Effects of Adenoviral Gene Transfer of c. elegans n−3 Fatty Acid Desaturase on the Lipid Profile and Growth of Human Breast Cancer Cells. Anticancer Res. 22, 537–543.
Morimoto, K.C., Van Eenennaam, A.L., DePeters, E.J., and Medrano, J.F. (2005) Endogenous Production of n−3 and n−6 Fatty Acids in Mammalian Cells, J. Dairy Sci. 88, 1142–1146.
Connor, W.E. (2000) Improtance of n−3 Fatty Acids in Health and Disease, Am. J. Clin. Nutr. 71, 171S-175S.
Bagga, D., Anders, K.H., Wang, H.J., and Glaspy, J.A. (2002) Long-Chain n−3-to-n−6 Polyunsaturated Fatty Acid Ratios in Breast Adipose Tissue from Women With and Without Breast Cancer. Nutr. Cancer 42, 180–185.
Maillard, V., Bougnoux, P., Ferrari, P., Jourdan, M.L., Pinault, M., Lavillonniere, F., Body, G., Le, F.O., and Chajes, V. (2002) n−3 and n−6 Fatty Acids in Breast Adipose Tissue and Relative Risk of Breast Cancer in a Case-Control Study in Tours, France. Int. J. Cancer 98, 78–83.
Robinson, L.E., Clandinin, M.T., and Field, C.J. (2002) The Role of Dietary Long-Chain n−3 Fatty Acids in Anti-cancer Immune Defense and R3230 AC Mammary Tumor Growth in Rats: Influence of Diet Fat Composition, Breast Cancer Res. Treat. 73, 145–160.
Reyes, N., Reyes, I., Tiwari, R., and Geliebter, J. (2004) Effect of Linoleic Acid on Proliferation and Gene Expression in the Breast Cancer Cell Line T47D. Cancer Lett. 209, 25–35.
Rose, D.P., and Connolly, J.M. (1999) Antiangiogenicity of Docosahexaenoic Acid and Its Role in the Suppression of Breast Cancer Cell Growth in Nude Mice. Int. J. Oncol. 15, 1011–1015.
Cave, W.T., Jr. (1997) Omega-3 Polyunsaturated Fatty Acids in Rodent Models of Breast Cancer, Breast Cancer Res. Treat. 46, 239–246.
Leaf, A., and Weber, P.C. (1987) A New Era for Science in Nutrition, Am. J. Clin. Nutr. 45, 1048–1053.
Akbar, M., Calderon, F., Wen, Z., and Kim, H.Y. (2005) Docosahe xaenoic Acid: A Positive Modulator of Akt Signaling in Neuronal Survival, Proc. Natl. Acad. Sci. USA 102, 10858–10863.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Ma, D.W.L., Ngo, V., Huot, P.S.P. et al. n-3 polyunsaturated fatty acids endogenously synthesized in fat-1 mice are enriched in the mammary gland. Lipids 41, 35–39 (2006). https://doi.org/10.1007/s11745-006-5067-9
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11745-006-5067-9