Breast Cancer Prevention by HormonallyInduced Mammary Gland Differentiation: The Role of a Novel Mammary Growth Inhibitor and Differentiation Factor

A mammary derived growth inhibitor related gene and a fatty acid binding protein 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 on breast epithelial cells and up-regulation of MRG expression in young nulliparous females can mimic pregnancy- and lactation-induced mammary gland differentiation and prevent breast cancer incidence. 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 of MRG transgenic mice resulted in the formation of alveolarAike structure. Consistent with the morphological change, expression of MRG also increased milk protein beta-casein expression in the gland. Our results suggest that MRG is a candidate mediator of the differentiating effect of pregnancy on breast epithelial cells.