Evidence from animal models and experimental human breast cancer cell growth in nude mice indicates that omega-6 fatty acids (n-6 FAs) stimulate growth and metastasis of mammary cancer, whereas omega-3 (n-3) FAs may exert an inhibitory effect. An understanding of the influence of different types of FAs on the biological behavior of human breast cancer cells is essential for the rational development of dietary interventions for disease prevention, and as adjuvant therapy after surgery. To this end, a series of studies is proposed utilizing a nude mouse model for human breast cancer cell metastasis. These will compare the effects of feeding diets containing different levels and proportions of n-6 and n-3 FAs on MDA-MB-435 cell growth at the primary (inoculation) site and on metastasis. Mechanistic studies will focus on (a) the role of the n-6 FA-derived eicosanoids in modulating tumor cell growth and expression of metastatic potential, and (b) on the inositol phospholipid signal transduction pathway. Prostaglandin and leukotrienes will be assayed directly in solid tumors, and [14C]-labelled n-6 FAs employed to assess their incorporation into membrane phospholipids of recultured primary and metastatic cells, the subsequent mobilization of arachidonate, and its utilization for eicosanoid production. The rates of inositol phospholipid hydrolysis, diacylglycerol production, and phospholipase C and protein kinase C Activities will be compared in cells from primary and metastatic tumors, which developed in mice from the various dietary groups.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA053124-03
Application #
2095202
Study Section
Metabolic Pathology Study Section (MEP)
Project Start
1992-08-01
Project End
1996-07-31
Budget Start
1994-08-01
Budget End
1996-07-31
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Institute for Cancer Prevention
Department
Type
DUNS #
City
Valhalla
State
NY
Country
United States
Zip Code
10595
Rose, D P; Connolly, J M (2000) Regulation of tumor angiogenesis by dietary fatty acids and eicosanoids. Nutr Cancer 37:119-27
Connolly, J M; Gilhooly, E M; Rose, D P (1999) Effects of reduced dietary linoleic acid intake, alone or combined with an algal source of docosahexaenoic acid, on MDA-MB-231 breast cancer cell growth and apoptosis in nude mice. Nutr Cancer 35:44-9
Rose, D P; Connolly, J M (1999) Omega-3 fatty acids as cancer chemopreventive agents. Pharmacol Ther 83:217-44
Rose, D P; 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 15:1011-5
Morse-Gaudio, M; Connolly, J M; Rose, D P (1998) Protein kinase C and its isoforms in human breast cancer cells: relationship to the invasive phenotype. Int J Oncol 12:1349-54
Connolly, J M; Rose, D P (1998) Enhanced angiogenesis and growth of 12-lipoxygenase gene-transfected MCF-7 human breast cancer cells in athymic nude mice. Cancer Lett 132:107-12
Rose, D P; Connolly, J M; Liu, X H (1997) Fatty acid regulation of breast cancer cell growth and invasion. Adv Exp Med Biol 422:47-55
Rose, D P (1997) Dietary fatty acids and prevention of hormone-responsive cancer. Proc Soc Exp Biol Med 216:224-33
Rose, D P (1997) Effects of dietary fatty acids on breast and prostate cancers: evidence from in vitro experiments and animal studies. Am J Clin Nutr 66:1513S-1522S
Rose, D P (1997) Dietary fatty acids and cancer. Am J Clin Nutr 66:998S-1003S

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