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

We have previously identified and characterized a novel tumor growth inhibitor and a fatty acid binding protein in human mammary gland and named it as Mammary derived growth inhibitor Related Gene MRG. MRG has tumor-suppressing activities; it inhibits breast cancer cell growth in vitro and tumor growth in vivo. Here, the MRG expression on mammary gland and the effects of MRG on mammary gland differentiation were investigated. MRG protein expression was associated with human mammary gland differentiation 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 resulted in a differentiated morphology and stimulation of beta-casein expression. In vivo studies using MMTV/MRG transgenic model also indicated an increased lobulo- alveoli in the gland from the MRG transgenic mice. Our results suggest that MRG is a candidate mediator of the differentiating effect of pregnancy on breast epithelial cells.
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