Research Papers:

Accelerated hepatocellular carcinoma development in CUL4B transgenic mice

Jupeng Yuan, Baichun Jiang, Aizhen Zhang, Yanyan Qian, Haining Tan, Jiangang Gao, Changshun Shao and Yaoqin Gong _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2015; 6:15209-15221. https://doi.org/10.18632/oncotarget.3829

Metrics: PDF 2526 views  |   HTML 2570 views  |   ?  


Jupeng Yuan1, Baichun Jiang1, Aizhen Zhang2, Yanyan Qian1, Haining Tan1, Jiangang Gao2, Changshun Shao1 and Yaoqin Gong1

1 Key Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, China

2 Key Laboratory of Experimental Teratology, Ministry of Education, Shandong University School of Life Science, Jinan, China

Correspondence to:

Baichun Jiang, email:

Yaoqin Gong, email:

Keywords: CUL4B transgenic mice, DEN, HCC, ROS, proliferation

Received: January 29, 2015 Accepted: March 26, 2015 Published: April 14, 2015


Cullin 4B (CUL4B) is a component of the Cullin 4B-Ring E3 ligase (CRL4B) complex that functions in proteolysis and in epigenetic regulation. CUL4B possesses tumor-promoting properties and is markedly upregulated in many types of human cancers. To determine the role of CUL4B in liver tumorigenesis, we generated transgenic mice that expressed human CUL4B in livers and other tissues and evaluated the development of spontaneous and chemically-induced hepatocellular carcinomas. We observed that CUL4B transgenic mice spontaneously developed liver tumors at a high incidence at old ages and exhibited enhanced DEN-induced hepatocarcinogenesis. There was a high proliferation rate in the livers of CUL4B transgenic mice that was accompanied by increased levels of Cdk1, Cdk4 and cyclin D1 and decreased level of p16. The transgenic mice also exhibited increased compensatory proliferation after DEN-induced liver injury, which was accompanied by activation of Akt, Erk, p38 and NF-κB. We also found that Prdx3 was downregulated and that DEN induced a higher level of reactive oxygen species in the livers of transgenic mice. Together, our results demonstrate a critical role of CUL4B in hepatocarcinogenesis in mice.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 3829