Serine/Threonine Kinase Pim-2 Promotes Liver Tumorigenesis Induction Through Mediating Survival and Preventing Apoptosis of Liver Cell

Background. It has been proven that serine/threonine kinase pim-2 mediates cell survival and prevents apoptosis in hematopoietic system tumors and lymphomas, but its role in so lid organ tumor induction is still unclear. In this study, we investigated its effects and underlying mechanisms in tumorigenesis of hepatocellular carcinoma. Methods. We first examined the pim-2 gene expression and its protein levels in human bepatocellular carcinoma, paired noncancerous liver, and normal liver tissues. Then, we cultured human liver cancer cells and immortalized liver cells to examine the effects of pim-2 gene on the cell, viability, growth, and apoptosis in different culture conditions. For further investigation of the molecular events in the pim-2 signal pathway, we also explored pim-2 kinase activity on phosphorylation of the two downstream signal mediators: 4E-BP1 and Bad. Results. Pim-2 gene and protein were notably expressed in human liver cancer tissues and HepG2 cells. The ectopic pim-2 overexpressing L02 cells were able to survive in interleukin-3 (IL-3)-deprived circumstance but not in glucose-free medium. Compared with HepG2 cells, pim-2 knock-down HepG2 cells lost survival ability in IL-3 starvation medium. In pim-2 expressing cells, both the total protein expressions of 4E-BP1 and Bad were kept stable; however, their phosphorylated patterns were notably increased. Conclusions. Our results indicate that pim-2 acts as a pro-survival kinase to inhibit apoptosis and keep liver cell survival in IL-3-deprived medium. Pim-2 might participate in the tumorigenesis of hepatocellular carcinoma induction through its downstream molecules 4E-BP1 and Bad. (C) 2009 Elsevier Inc. All rights reserved.