ANTITUMOR-ACTIVITY OF THE NOVEL HUMAN BREAST-CANCER GROWTH INHIBITOR,MAMMARY-DERIVED GROWTH INHIBITOR-RELATED GENE, MRG

A novel human tumor growth inhibitor was identified by differential cD NA sequencing, The predicted amino acid sequence of this tumor-suppres sing factor has a significant sequence homology to mouse mammary-deriv ed growth inhibitor and thus was named mammary-derived growth inhibito r-related gene (MRG). MRG was found to be expressed in normal and beni gn human breast tissues but not in breast carcinomas, In situ hybridiz ation analysis demonstrated a stage-specific MRG expression as follows . MRG was barely detectable in breast carcinomas, showed partial and w eak expression in benign hyperplasia, but was expressed at a high leve l in normal breast epithelial cells. To determine if MRG can modulate in vivo growth of human breast cancers, we transfected a full-length M RG cDNA into MDA-MB-231 human breast cancer cells and studied the orth otopic growth of MRG transfectants versus control transfectants in the mammary fat pad of athymic nude mice. Overexpression of MRG in human breast cancer cells significantly suppressed cell proliferation in vit ro and tumor growth in an orthotopic nude mouse model. These results s uggest that MRG has tumor-suppressing activity, and the loss of MRG ex pression map be involved in the development and progression of breast cancer.