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

Naofumi Mukaida1, Ying-Ying Wang, Ying-Yi Li

  • 1Division of Molecular Bioregulation, Cancer Microenvironment Research Program, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. naofumim@kenroku.kanazawa-u.ac.jp

Cancer Science
|April 27, 2011
PubMed

Insights

Provirus integrating site Moloney murine leukemia virus-3 (Pim-3) kinase promotes cancer cell proliferation and survival. Inhibiting Pim-3 kinase may offer a novel therapeutic strategy for treating cancers like liver, pancreas, and colon carcinoma.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Pim-3 is a serine/threonine kinase in the Pim family, related to Ca(2+)/calmodulin-dependent protein kinase (CaMK).
  • Pim-3 shares functions with Pim-1 and Pim-2, including apoptosis prevention, cell survival promotion, and enhanced cell proliferation in normal and malignant cells.
  • While expressed in vital organs, Pim-3-deficient mice show minimal phenotypic changes, suggesting physiological dispensability.

Purpose of the Study:

  • To investigate the role of Pim-3 in cancer development and proliferation.
  • To evaluate Pim-3 as a potential target for cancer therapy.

Main Methods:

  • Analysis of Pim-3 expression in various cancer tissues.
  • Studies in mice with liver-specific Pim-3 expression treated with hepatocarcinogens.
  • In vitro studies inhibiting Pim-3 expression in hepatocellular, pancreatic, and colon carcinoma cell lines.
  • In vivo xenograft studies using a human pancreatic cancer cell line treated with a Pim-3 kinase inhibitor.

Main Results:

  • Pim-3 expression is elevated in several cancers, especially endoderm-derived organs.
  • Pim-3 acts as a promoter, not an initiator, in hepatocellular carcinoma development.
  • Inhibition of Pim-3 expression reduced in vitro proliferation of liver, pancreatic, and colon cancer cells by inducing apoptosis.
  • A Pim-3 kinase inhibitor demonstrated efficacy in an in vivo pancreatic cancer xenograft model with no major adverse effects.

Conclusions:

  • Pim-3 kinase plays a significant role in promoting cancer cell proliferation and survival.
  • Targeting Pim-3 kinase represents a promising strategy for developing novel anti-cancer molecular therapies.

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