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.

• Keywords: TIS21/BTG2/PC3;FoxM1;Cyclin B1;Hepatocarcinogenesis