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

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Abstract
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 G2/M phase of the cell cycle. This G2/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.