TUMOR-SUPPRESSOR ACTIVITY OF THE GENE ENCODING MAMMARY-DERIVED GROWTHINHIBITOR

The gene encoding mammary-derived growth inhibitor (MDGI), a protein p reviously purified from bovine mammary gland and shown to have modest antiproliferative activity for human breast cancer cells Bt vitro, is demonstrated to function as a potent tumor suppressor gene, Human brea st cancer cells transfected with a MDGI expression construct exhibited differentiated morphology, reduced proliferation rate, reduced clonog enicity in soft agar, and reduced tumorgenicity in nude mice relative to mock transfected or untransfected controls, We mapped the human hom ologue of this gene to chromosome 1p33-35, a locus previously shown to exhibit frequent loss of heterozygosity in human breast cancer, MDGI immunoreactivity was detected in epithelial cells of human breast tiss ue, but not on ductal carcinoma cells on the same sections, Our result s suggest that MDGI is a strong candidate for the distal 1p breast tum or suppressor gene, Furthermore, as prior reports have demonstrated th at MDGI is hormonally regulated in breast epithelial cells and maximal ly expressed at the time of maximal differentiated function (just prio r to lactation), MDGI is a candidate mediator of the differentiating e ffect of pregnancy on breast epithelial cells, which may be involved i n the protective effect of early parity on subsequent breast cancer in cidence.