生物
肝细胞
细胞凋亡
癌症研究
癌基因
蛋白激酶B
肝细胞生长因子
磷酸化
细胞生长
内分泌学
内科学
程序性细胞死亡
细胞周期
细胞生物学
生物化学
受体
医学
体外
作者
Sarah A. Comerford,David E. Clouthier,Elizabeth A Hinnant,Robert E. Hammer
出处
期刊:Oncogene
[Springer Nature]
日期:2003-04-24
卷期号:22 (16): 2515-2530
被引量:7
标识
DOI:10.1038/sj.onc.1206259
摘要
Mice expressing SV40 T-Antigen in liver under control of the phosphoenolpyruvate carboxykinase promoter were generated. By altering the carbohydrate content of the diet, TAg expression, the rate of hepatocyte proliferation and apoptosis, and hence hepatocarcinogenesis, could be regulated. Carbohydrate-mediated suppression of TAg resulted in slow hepatic growth that progressed to focal hepatocellular carcinoma (HCC) after a long latency period. In contrast, induction of TAg by feeding mice a low carbohydrate diet resulted in massive hepatomegaly that progressed rapidly to diffuse multifocal HCC. Hepatic TAg expression could be efficiently repressed by switching mice from the low to the high-carbohydrate diet, which if instigated prior to the development of HCC, resulted in rapid regression through a p53-independent reduction in hepatocyte proliferation and an increase in hepatocyte apoptosis. Although liver growth was accompanied by compensatory hepatocyte apoptosis, an apoptotic deficit developed following chronic exposure to high levels of TAg. This was associated with Akt phosphorylation and increased expression of the antiapoptotic molecules bfl-1/A1, TIAP, and A20. Mice were resistant to Fas-induced hepatocellular apoptosis due to severely impaired caspase activation and failed activation of the mitochondrial amplification loop. This model will be useful to investigate oncogene-mediated disruption of the cell cycle and apoptosis, and to determine which processes constitute fixed, or reversible aspects of the tumorigenic process.
科研通智能强力驱动
Strongly Powered by AbleSci AI