Induction of mammary differentiation by mammary-derived growth inhibitor-related gene that interacts with an omega-3 fatty acid on growth inhibition of breast cancer cells

We previously identified and characterized a novel tumor growth inhibitor a nd a fatty acid-binding protein in human mammary gland and named it the mam mary-derived growth inhibitor-related gene (MRG), Here, the effects of MRG on mammary gland differentiation and its interaction with omega -3 polyunsa turated fatty acids (omega -3 PUFAs) on growth inhibition were investigated . MRG protein expression was associated with human mammary gland differenti ation, with the highest expression observed in the differentiated alveolar mammary epithelial cells from the lactating gland. 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 resulte d in a differentiated morphology and stimulation of beta -casein expression , Treatment of human breast cancer cells with the omega -3 PUFA docosahexae noic acid resulted in a differential growth inhibition proportional to thei r MRG expression. MRG-transfected tells or MRG protein treated cells were m uch more sensitive to docosahexaenoic acid-induced growth inhibition than M RG-negative or untreated control cells, Our results suggest that MRG is a c andidate mediator of the differentiating effect of pregnancy on breast epit helial cells and may play a major role in omega -3 PUFA-mediated tumor supp ression.