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

フォーマット:

論文

責任表示:

Wu, Yu ; Wang, Ying Ying ; Nakamoto, Yasunari ; Li, Ying-Yi ; Baba, Tomohisa ; Kaneko, Shuichi ; Fujii, Chifumi ; Mukaida, Naofumi

言語:

英語

出版情報:

Nature Publishing Group, 2010-04-01

著者名:

Wu, Yu

Wang, Ying Ying

Nakamoto, Yasunari

Li, Ying-Yi

Baba, Tomohisa

Kaneko, Shuichi

Fujii, Chifumi

Mukaida, Naofumi

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掲載情報:

Oncogene

ISSN:

0950-9232      

巻:

29

通号:

15

開始ページ:

2228

終了ページ:

2237

バージョン:

author

概要:

金沢大学がん研究所<br />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. © 2010 Macmillan Publishers Limited. All rights reserved. 続きを見る

URL:

http://hdl.handle.net/2297/24282