Omega-3 Fatty Acids and a Novel Mammary Derived Growth Inhibitor Fatty Acid Binding Protein MRG in Suppression of Mammary Tumor

摘要

A mammary derived growth inhibitor related gene (MRG) was previously identified and characterized. The present study is to test the hypothesis that MRG is a candidate mediator of the differentiating effect of pregnancy and lactation of breast epithelial cells and a candidate mediator of the tumor suppressing effect of n-3 fatty acid DHA on mammary tumors. MRG induces differentiation of mammary epithelial cells in vitro and its expression is associated with mammary differentiation. Overexpression of MRG in human breast cancer cells induced differentiation with changes in cellular morphology and a significant increase in the production of lipid droplets. Treatment of mouse mammary gland in organ culture with MRG protein resulted in a differentiated morphology and stimulation of beta-casein expression. While there was no lobulo- alveolar structure in control virgin mice, expression of MRG transgene in the mammary gland in the transgenic mouse resulted in the formation of alveolar-like structure. Consistent with the morphological change, expression of MRG also increased milk protein beta-casein expression in the gland. Treatment of human breast cancer cells with w-3 PUFA DHA resulted in a differential growth inhibition proportional to their MRG expression. MRG transfected cells or MRG protein treated cells were much more sensitive to DHA-induced growth inhibition compared with MRG negative or control non-treated cells. Our results suggest that MRG is a candidate mediator of the differentiating effect of pregnancy on breast epithelial cells and may play a major role in w-3 PUFA-mediated tumor suppression.