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Oncogene. 2010 Apr 15;29(15):2228-37. doi: 10.1038/onc.2009.504. Epub 2010 Jan 18.

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

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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.


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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