INTERACTION OF OMEGA 3 FATTY ACIDS AND NOVEL FATTY ACID

Long Island Jewish Medical Center, New Hyde Park NY

Investigators

Abstract

There is an increasing public interest in the dietary supplement of omega-3 polyunsaturated fatty acids (PUFAs) with respect to their beneficial effects on reduction of cardiovascular diseases and certain types of cancer. It is well established the omega-3 PUFAs such as DHA and EPA have a tumor suppressing effect and prevents mammary tumors in the animal models. Currently, the cellular interactions by which omega-3 PUFAs exert their tumor suppression are poorly understood. Within this content, a novel mammary derived growth inhibitor and a fatty acid binding protein (FABP) has recently been identified, characterized, and named as Mammary derived growth inhibitor Related Gene MRG. Being as a new member of FABP family, MRG has a highest binding affinity to DHA. Expression of MRG was lost during breast cancer malignant progression and transfection of MRG gene to human breast cancer cells dramatically suppressed tumor cell growth in vitro and in vivo in an orthotopic nude mouse model. MRG induced the differentiation of breast cancer cells, and its expression was associated with mammary gland differentiation with the highest expression towards the terminally differentiated alveolar mammary epithelial cells from the lactating gland. Treatment of human breast cancer cells with DHA resulted in a differential growth inhibition in the cells as to their MRG expression; MRG positive cells were much more sensitive to DHA-induced growth inhibition compared with MRG negative cells. The present application is to test the hypothesis that omega-3 PUFAs-induced growth inhibition and tumor suppression is mediated in part by their interaction with fatty acid binding protein MRG. SP1. In vitro study of differential growth inhibition of DHA and EPA on human breast cancer cells in respect to their MRG expression. SP2. In vivo study of tumor suppressing activities of DHA and EPA on MRG positive tumors vs. MRG negative tumors and on MRG gene transferred mice vs. control mice. These studies will help further define the mechanisms underlying the tumor suppression activity of omega-3 PUFAs and provide a potential new surrogate endpoint to for predict tumor suppressive response to omega-3 PUFAs, which may advance a new paradigm for breast cancer intervention.