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

BACKGROUND. Mxi1, an antagonist of c-Myc, maps to human chromosome 10q24-q2 5, a region altered in a substantial fraction of prostate tumors. Mice defi cient for Mail exhibit significant prostate hyperplasia. We studied the abi lity 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 prolifera tion, soft agar colony formation, and cell cycle distribution. To explore m echanisms of Mxi1-induced growth arrest, we performed gene expression analy sis. RESULTS. AdMxi1 infection resulted in reduced cell proliferation, reduced s oft agar colony formation: and a higher proportion of cells in the G(2)/M p hase of the cell cycle. This G(2)/M growth arrest was associated with eleva ted levels of cyclin B, and reduced levels of c-MYC and MDM2. CONCLUSIONS. The ability of AdMxi1 to suppress prostate tumor cell prolifer ation supports a role for Mxi1 loss in the pathogenesis of a subset of huma n prostate canters. Prostate 47:194-204, 2001. (C) 2001 Wiley-Liss, Inc.