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

Gong, Jianping; Wang, Jinjing; Ren, Ke; Liu, Chang'an; Li, Bo; Shi, Yujun

doi:10.1016/j.jss.2008.03.033

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Volume 153, Issue 1 , Pages 17-22, 1 May 2009

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

Jianping Gong, Ph.D.
- Department of General Surgery, the 2nd College of Clinical Medicine and the 2nd Affiliated Hospital of Chongqing University of Medical Science, Chongqing, China
Jinjing Wang, Ph.D.
- Laboratory of Transplant Immunology, Western China Hospital, Sichuan University, Chengdu, China
Ke Ren, M.Med.
- Department of General Surgery, the 2nd College of Clinical Medicine and the 2nd Affiliated Hospital of Chongqing University of Medical Science, Chongqing, China
Chang'an Liu, M.B.
- Department of General Surgery, the 2nd College of Clinical Medicine and the 2nd Affiliated Hospital of Chongqing University of Medical Science, Chongqing, China
Bo Li, M.D.
- Department of General Surgery, the 2nd College of Clinical Medicine and the 2nd Affiliated Hospital of Chongqing University of Medical Science, Chongqing, China
Yujun Shi, Ph.D.
- Department of General Surgery, the 2nd College of Clinical Medicine and the 2nd Affiliated Hospital of Chongqing University of Medical Science, Chongqing, China
- Laboratory of Transplant Immunology, Western China Hospital, Sichuan University, Chengdu, China
- To whom correspondence and reprint requests should be addressed at Laboratory of Transplant Immunology, Western China Hospital, Sichuan University, 1^# Keyuan 4 Road, Chengdu, 610041, PR. China

Received 15 December 2007 published online 12 May 2008.

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 solid 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 hepatocellular 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.

Key Words: pim-2, hepatocellular carcinoma, apoptosis, tumorigenesis