Mxi1, a Myc antagonist, suppresses proliferation of DU145 human prostate cells

BACKGROUND: Mxi1, an antagonist of c-Myc, maps to human chromosome 10q24-q25, a region altered in a substantial fraction of prostate tumors. Mice deficient for Mxi1 exhibit significant prostate hyperplasia. We studied the ability of Mxi1 to act as a growth suppressor in prostate tumor cells. METHODS: We infected DU145 prostate carcinoma cells with an Mxi1-expressing adenovirus (AdMxi1) in vitro, and measured Mxi1 expression, cell proliferation, soft agar colony formation, and cell cycle distribution. To explore mechanisms of Mxi1-induced growth arrest, we performed gene expression analysis. RESULTS: AdMxi1 infection resulted in reduced cell proliferation, reduced soft agar colony formation, and a higher proportion of cells in the G(2)/M phase of the cell cycle. This G(2)/M growth arrest was associated with elevated levels of cyclin B, and reduced levels of c-MYC and MDM2. CONCLUSIONS: The ability of AdMxi1 to suppress prostate tumor cell proliferation supports a role for Mxi1 loss in the pathogenesis of a subset of human prostate cancers. Prostate 47:194-204, 2001.