• Open Access

Roles of Pim-3, a novel survival kinase, in tumorigenesis

Authors

  • Naofumi Mukaida,

    Corresponding author
    1. Division of Molecular Bioregulation, Cancer Microenvironment Research Program, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
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  • Ying-Ying Wang,

    1. Division of Molecular Bioregulation, Cancer Microenvironment Research Program, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
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  • Ying-Yi Li

    1. Division of Molecular Bioregulation, Cancer Microenvironment Research Program, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
    2. Cancer Research Laboratory, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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To whom correspondence should be addressed.
E-mail: naofumim@kenroku.kanazawa-u.ac.jp

Abstract

Pim-3 is a member of the Provirus integrating site Moloney murine leukemia virus (Pim) family, which belongs to the Ca2+/calmodulin-dependent protein kinase (CaMK) group and exhibits serine/threonine kinase activity. Similar to other members of the Pim family (i.e. Pim-1 and Pim-2), Pim-3 can prevent apoptosis and promote cell survival and protein translation, thereby enhancing cell proliferation of normal and malignant cells. Pim-3 is expressed in vital organs, such as the heart, lung, and brain. However, minimal phenotypic changes in Pim-3-deficient mice suggest that Pim-3 may be physiologically dispensable. Pim-3 expression is enhanced in several cancer tissues, particularly those of endoderm-derived organs, including the liver, pancreas, colon, and stomach. The development of hepatocellular carcinoma is accelerated in mice expressing the Pim-3 gene selectively in the liver only when these mice are treated with a hepatocarcinogen, indicating that Pim-3 can act as a promoter but not as an initiator. Moreover, inhibition of Pim-3 expression can retard in vitro cell proliferation of hepatocellular, pancreatic, and colon carcinoma cell lines by promoting cell apoptosis. Furthermore, a Pim-3 kinase inhibitor has been reported to inhibit cell proliferation in an in vivo xenograft model using a human pancreatic cancer cell line without inducing any major adverse effects. Thus, Pim-3 kinase may be a candidate molecule for the development of molecular targeting drugs against cancer. (Cancer Sci 2011; 102: 1437–1442)

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