Two-stage model of chemically induced hepatocellular carcinoma in mouse.
The aim of this study was to develop an efficient and reproducible mouse model for hepatocellular carcinoma (HCC) research and assess the expression of two proto-oncogenes (c-myc and N-ras) and tumor suppressor gene p53 in the carcinogenic process. In this study, we found that diethylnitrosamine initiation with CCl4 and ethanol promotion could induce a short-term, two-stage liver carcinogenesis model in male BALB/c mice, the process of hepatocarcinogenesis including liver damage, liver necrosis/cell death, liver inflammation, liver proliferation, liver hyperplasia, liver steatosis, and liver cirrhosis and hepatocellular nodules, which mimicked the usual sequence of events observed in human HCC. We also identified that the increase in expression of the p53 gene is related to the proliferation of hepatocytes, whereas overexpression of the c-myc and N-ras genes is associated with hepatocarcinogenesis. This animal model may serve as a basis for recapitulating the molecular pathogenesis of HCC seen in humans.
Biomedical Research Center, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China.
Min
M
Luo
Fan
F
Yang
Sheng-xin
SX
Huang
Zhi-peng
ZP
Kuang
Xiao-ling
XL
Luo
Yuan-dong
YD
Li
Ji-ning
JN
Wu
Yu-an
YA
Xie
D000818:Animals; D017209:Apoptosis; D002251:Carbon Tetrachloride / Q000008:administration & dosage; D063646:Carcinogenesis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000473:pathology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004052:Diethylnitrosamine / Q000008:administration & dosage; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology*; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D004052:Diethylnitrosamine; D002251:Carbon Tetrachloride; D020559:Monomeric GTP-Binding Proteins; C586503:Nras protein, mouse