Biomedical Research Center, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China.
Oncol Res. 2013;20(11):517-28. doi: 10.3727/096504013X13747716581336.
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.
本研究旨在建立一种高效且可重现的用于肝细胞癌（HCC）研究的小鼠模型，并评估两种原癌基因（c-myc 和 N-ras）和肿瘤抑制基因 p53 在致癌过程中的表达。在本研究中，我们发现二乙基亚硝胺（DEN）引发联合 CCl4 和乙醇促进可诱导雄性 BALB/c 小鼠的短期、两阶段肝致癌发生模型，肝致癌发生过程包括肝损伤、肝坏死/细胞死亡、肝炎症、肝增殖、肝增生、肝脂肪变性、肝硬变和肝细胞结节，这模拟了在人类 HCC 中观察到的通常的事件序列。我们还发现，p53 基因表达的增加与肝细胞的增殖有关，而 c-myc 和 N-ras 基因的过表达与肝癌发生有关。该动物模型可能作为模拟人类 HCC 分子发病机制的基础。
