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

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概要

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• 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, doi: 10.1111/j.1349-7006.2011.01966.x, 2011) © 2011 Japanese Cancer Association.

• Japanese Cancer Association = 日本癌学会の論文
• 2011-08-10

著者

• Mukaida Naofumi

  Division Of Molecular And Bioregulation Cancer Research Institute Kanazawa University

• Li Ying-yi

  Division Of Molecular Bioregulation Cancer Research Institute Kanazawa University

• Mukaida Naofumi

  Division Of Molecular Bioregulation Cancer Microenvironment Research Program Cancer Research Institute Kanazawa University

• WANG Ying-Ying

  Division of Molecular Bioregulation, Cancer Microenvironment Research Program, Cancer Research Institute, Kanazawa University

• Wang Ying-ying

  Division Of Molecular Bioregulation Cancer Microenvironment Research Program Cancer Research Institute Kanazawa University

• Li Ying-yi

  Division Of Molecular Bioregulation Cancer Microenvironment Research Program Cancer Research Institute Kanazawa University

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