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World J Gastroenterol. Jul 28, 2014; 20(28): 9392-9404
Published online Jul 28, 2014. doi: 10.3748/wjg.v20.i28.9392
Pathophysiological roles of Pim-3 kinase in pancreatic cancer development and progression
Ying-Yi Li, Naofumi Mukaida
Ying-Yi Li, Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai 200433, China
Ying-Yi Li, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200433, China
Ying-Yi Li, Division of Molecular Bioregulation, Cancer Microenvironment Research Program, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Japan
Naofumi Mukaida, Division of Molecular Bioregulation, Cancer Microenvironment Research Program, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Japan
Author contributions: Li YY contributed to manuscript writing and final revision of the article; Mukaida N contributed to overall design, manuscript writing, and final revision of the article.
Supported by The National Science Foundation of China (in part), No. 30973476 and No. 812727
Correspondence to: Naofumi Mukaida, MD, PhD, Professor, Division of Molecular Bioregulation, Cancer Microenvironment Research Program, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. mukaida@staff.kanazawa-u.ac.jp
Telephone: +81-76-2646735 Fax: +81-76-2344520
Received: October 25, 2013
Revised: January 22, 2014
Accepted: March 8, 2014
Published online: July 28, 2014
Abstract

Pim-3 is a member of the provirus integration site for Moloney murine leukemia virus (Pim) family proteins that exhibit serine/threonine kinase activity. Similar to the other Pim kinases (Pim-1 and Pim-2), Pim-3 is involved in many cellular processes, including cell proliferation, survival, and protein synthesis. Although Pim-3 is expressed in normal vital organs, it is overexpressed particularly in tumor tissues of endoderm-derived organs, including the liver, pancreas, and colon. Silencing of Pim-3 expression can retard in vitro cell proliferation of hepatocellular, pancreatic, and colon carcinoma cell lines by promoting cell apoptosis. Pim-3 lacks the regulatory domains similarly as Pim-1 and Pim-2 lack, and therefore, Pim-3 can exhibit its kinase activity once it is expressed. Pim-3 expression is regulated at transcriptional and post-transcriptional levels by transcription factors (e.g., Ets-1) and post-translational modifiers (e.g., translationally-controlled tumor protein), respectively. Pim-3 could promote growth and angiogenesis of human pancreatic cancer cells in vivo in an orthotopic nude mouse model. Furthermore, a Pim-3 kinase inhibitor inhibited cell proliferation when human pancreatic cancer cells were injected into nude mice, without inducing any major adverse effects. Thus, Pim-3 kinase may serve as a novel molecular target for developing targeting drugs against pancreatic and other types of cancer.

Keywords: Serine/threonine kinase, Pancreatic cancer, Ets-1, Translationally controlled tumor protein, c-Myc, Vascular endothelium growth factor, Apoptosis, Cell cycle

Core tip: The present review describes the current knowledge on the roles of Pim-3 in pancreatic cancer development and progression, and provides the possibility for Pim-3 as a therapeutic target in human pancreatic cancer.