Pim-2 upregulation: biological implications associated with disease progression and perinueral invasion in prostate cancer.

BACKGROUND: The serine/threonine kinase Pim-2 acts as a transcriptionally regulated apoptotic inhibitor and is implicated in prosurvival. Pim-2 has been implicated in many apoptotic pathways.
MATERIALS AND METHODS: Silencer validated short interfering RNA (siRNA) to Pim-2, Silencer GAPDH siRNA, and one scrambled siRNA for eliciting RNAi were transfected separately into DU-145/DRG in vitro model. Total RNA was extracted, purified, and validated by Quantitative RT-PCR 48 hr after transfection. The effects of Pim-2 silencing in vitro were evaluated by Western blot and immunofluroscence and collaborated with Ki-67 and TUNEL. The first microarrays (0.6 mm) had 640 radical prostatectomies while the second array (2 mm) used 226 perineural invasion (PNI) cases.
RESULTS: mRNA level of Pim-2 in experimental samples was 99% decreased. The experimental samples (mean 7.6 +/- 0.52%) had significantly higher apoptosis than controls (mean 0.89 +/- 0.014%) (P = 0.000). Conversely, proliferation (Ki-67 index) of the experimental samples (mean 57.1 +/- 3.94%) was lower than controls(mean 64.7 +/- 3.1%), but not significant (P = 0.0979). Both nuclear and cytoplasmic Pim-2 were increased in PNI than in prostate cancer (PCa) away from the nerve. Increased nuclear Pim-2 in PCa was associated with many established prognostic factors. Increased Pim-2 levels (nuclear or cytoplasmic) also correlated with NFkappaB nuclear translocation, higher proliferation, and reduced apoptosis. Higher level of nuclear Pim-2 in the PCa was associated with higher risk of biochemical recurrence (HR: 1.021-2.419, P = 0.0399).
CONCLUSION: Pim-2 is an important prosurvival gene, which might result in activation of enhanced anti-apoptotic pathway, leading to a more aggressive phenotype of PCa. Pim-2 may become a target for novel therapeutic strategies. Copyright 2005 Wiley-Liss, Inc