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Journal of the Korean Liver Cancer Study 2011;11(2):130-135.
Published online September 30, 2011.
The Role of TIS21/BTG2/PC3 during Hepatocarcinogenesis
Tae Jun Park
Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon, Korea
Correspondence:  Tae Jun Park,
Email: park64@ajou.ac.kr
Copyright ©2011 by The Korean Liver Cancer Association
Abstract
A functional and biochemical features of TIS21(/BTG2/PC3) was explored in hepatocarcinogenesis. Growth of hepatocellular carcinoma (HCC), developed by a single injection of diethylnitrosamine (DEN) was significantly higher in the TIS21 knockout mice at 9 months. Expression of BTG2/TIS21 was significantly lower in both human and mouse hepatocellular carcinoma than in the surrounding normal tissues. Over-expression of TIS21 inhibited cell proliferation and tumorigenic potential of Huh7 hepatoma cells. At the molecular mechanistic level, TIS21 inhibited FoxM1 phosphorylation, by reducing cyclin B1-cdk1 activity. Furthermore, TIS21 inhibited FoxM1 transcriptional activity. In conclusion, TIS21 negatively regulated hepatocarcinogenesis in part by disruption of the FoxM1-cyclin B1 regulatory loop, thereby inhibiting proliferation of transformed cells developed in mouse and human livers.
Key Words: TIS21/BTG2/PC3; FoxM1; Cyclin B1; Hepatocarcinogenesis
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