Influence of PUFA on immune cell MAPK: A prospective cancer biomarker

KE Sakera, BE Cowinga, WR Hucklea, I Paetau-Robinsonb

VA-MD Regional College of Veterinary Medicinea,Virginia Tech, Blacksburg, VA and Hill’s Pet Nutritionb, Inc, Topeka, KS.

AIM: Feline and human mammary cancers possess similar characteristics of development and progression, suggesting the appropriateness of the feline as a model for human breast cancer. Mitogen activated protein kinase (MAPK) and its effectors are associated with the growth and stage of breast cancer, and may be modulated via the action of polyunsaturated fatty acids (PUFA). We investigated if MAPK could be detected in white blood cell (WBC) populations, using a feline model, and if its activity was influenced by dietary (n-6):(n-3) PUFA ratio. METHODS: WBC were stimulated with 13-phorbol-15-myristateacetate and analyzed for MAPK activity via flow cytometry and immunoblotting, using phospho- and total MAPK monoclonal antibodies. RESULTS: MAPK was detectable in all study subjects. Across all time periods (P=0.02) and within each time period, the percent of immune cells staining positively for active MAPK was altered. Increased dietary (n-6):(n-3) PUFA ratio was associated with increased active MAPK in WBC. Active MAPK in WBC subpopulations appeared to be influenced by age of subject and time on diet. By week 12, the granulocyte population responded (P=0.0004) to changes in dietary (n-6):(n-3) PUFA. The mononuclear cell population responded (P=0.0069) to dietary PUFA alterations by week 24. CONCLUSION: In the feline model, dietary PUFA ratio and age influenced MAPK activity in immune cells. This implies that immune cell MAPK can be influenced by PUFA; and the feline may be an appropriate model for studying MAPK as a mammary cancer biomarker.

KEY WORDS: Key Words n6n3 fatty acids, mammary tumor, breast cancer, feline, model.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Dietary Influences.