Pim-1 is an oncogenic kinase that cooperates with c-Myc in oncogenesis. We have previously shown that Pim-1 overexpression can induce genomic instability in prostate epithelial cells. c-Myc expression also has been shown to induce genomic instability when p53 function is lost in 32D cells, which is a diploid murine myeloid cell line. To determine whether Pim-1 and c-Myc can cooperate to induce genomic instability, we estabilished stable prostate epithelial cell lines that overexpress both Pim-1 and c-Myc. There were no significant differences in cell proliferation or apoptosis in any of these cell lines even with stimulus such as TRAIL. However cell cycle profile analysis by FACS showed dramatic cooperation in induction of polyploidy between Pim-1 and c-Myc. Either Pim-1 or Myc alone induced modest increase of polyploidy cells (25.24%, 34.91% of >4N cells respectively) compared to control cell line (18.72%). However when Pim-1 and Myc were overexpressed simultaneously, the percentage of polyploidy cells was increased to 68.66%. We found that cyclin E expression level is significantly increased, and Cdc25C expression level is decreased in Myc overexpressing cells. We also found out that expression level of cyclin B1 is significantly increased in Pim-1 overexpressing cells. This increase is observed in early passage cells, suggesting that it is involved in genomic instability. Together our data suggest that Pim-1 and Myc can accelerate genomic instability by affecting different stage of cell cycles; Pim-1 affect G2/M phase, and Myc affect G1 /S phase

[Proc Amer Assoc Cancer Res, Volume 46, 2005]