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Accelerated hepatocellular carcinoma development in mice expressing the Pim-3 transgene selectively in the liver

Oncogene volume 29, pages 2228–2237 (2010)Cite this article

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Abstract

Pim-3, a proto-oncogene with serine/threonine kinase activity, was enhanced in hepatocellular carcinoma (HCC) tissues. To address the roles of Pim-3 in HCC development, we prepared transgenic mice that express human Pim-3 selectively in liver. The mice were born at a Mendelian ratio, were fertile and did not exhibit any apparent pathological changes in the liver until 1 year after birth. Pim-3-transgenic mouse-derived hepatocytes exhibited accelerated cell cycle progression. The administration of a potent hepatocarcinogen, diethylnitrosamine (DEN), induced accelerated proliferation of liver cells in Pim-3 transgenic mice in the early phase, compared with that observed for wild-type mice. Treatment with DEN induced lipid droplet accumulation with increased proliferating cell numbers 6 months after the treatment. Eventually, wild-type mice developed HCC with a frequency of 40% until 10 month after the treatment. Lipid accumulation was accelerated in Pim-3 transgenic mice with higher proliferating cell numbers, compared with that observed for wild-type mice. Pim-3 transgenic mice developed HCC with a higher incidence (80%) and a heavier burden, together with enhanced intratumoral CD31-positive vascular areas, compared with that observed for wild-type mice. These observations indicate that Pim-3 alone cannot cause, but can accelerate HCC development when induced by a hepatocarcinogen, such as DEN.

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Author notes

  1. C Fujii

    Present address: 5Present address, Department of Integrative Physiology, School of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto 390-8621, Japan.,

Authors and Affiliations

  1. Department of Hematology and Hematology research Laboratory, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, PR China

    Y Wu

  2. Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, 13-1 Takara-machi, Kanazawa, Japan

    Y Wu, Y Y Wang, Y-Y Li, T Baba, C Fujii & N Mukaida

  3. Department of Disease Control and Homeostasis, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, Japan

    Y Nakamoto & S Kaneko

  4. Researcher Center, Fudan University Cancer Hospital, Shanghai, PR China

    Y-Y Li

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Correspondence to N Mukaida.

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Wu, Y., Wang, Y., Nakamoto, Y. et al. Accelerated hepatocellular carcinoma development in mice expressing the Pim-3 transgene selectively in the liver. Oncogene 29, 2228–2237 (2010). https://doi.org/10.1038/onc.2009.504

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  • DOI: https://doi.org/10.1038/onc.2009.504

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