Novel mouse models of hepatocarcinogenesis with stepwise accumulation of genetic alterations.
Novel mouse models of hepatocarcinogenesis with stepwise accumulation of genetic alterations.
复制标题
具有逐步积累遗传改变的肝癌发生的新型小鼠模型。
DOI：
10.1159/000355244
复制
发表时间：
2013
影响因子：
2.3
通讯作者：
Masatoshi Kudo.
中科院分区：
文献类型：
--
作者：
Soo Ki Kim;Hiroyuki Marusawa;Yuji Eso;Tsutomu Chiba;Masatoshi Kudo.
肝细胞癌（HCC）是世界范围内最常见的癌症之一。各种危险因素参与肝癌的发生。其中，慢性炎症，包括主要由B型肝炎病毒和/或C型肝炎病毒感染引起的慢性肝炎和肝硬化，在HCC的发展中起着重要作用。另一方面，使用全基因组和外显子组测序对HCC进行的全面遗传分析显示，癌细胞具有大量的体细胞突变，这表明各种各样的遗传改变和由此产生的失调分子途径有助于HCC的发展。激活诱导的胞苷脱氨酶（AID）是一种核苷酸编辑酶，炎症反应诱导的AID异常表达通过多种肿瘤相关基因的遗传改变的积累促进肝癌的发生。AID在肝细胞系细胞中的组成型表达提供了新的小鼠模型，其通过逐步积累遗传改变来重现人HCC的肿瘤发生。
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Various risk factors are involved in hepatocarcinogenesis. Among them, chronic inflammation, including chronic hepatitis and cirrhosis mainly caused by hepatitis B virus and/or hepatitis C virus infection, plays an important role in HCC development. On the other hand, comprehensive genetic analyses of HCC using whole genome and exome sequencing revealed that cancer cells possess a large number of somatic mutations, suggesting that a wide variety of genetic alterations and the resultant dysregulated molecular pathways contribute to the development of HCC. Activation-induced cytidine deaminase (AID) is a nucleotide-editing enzyme, and aberrant expression of AID induced by inflammatory responses contributes to hepatocarcinogenesis via the accumulation of genetic alterations in various tumor-related genes. Constitutive expression of AID in hepatocyte-lineage cells provides novel mouse models that recapitulate the tumorigenesis of human HCC through stepwise accumulation of genetic alterations.