Over-expression of c-raf-1 proto-oncogene in liver cirrhosis and hepatocellular carcinoma
Over-expression of c-raf-1 proto-oncogene in liver cirrhosis and hepatocellular carcinoma
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DOI：
10.1016/j.hepres.2004.02.009
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发表时间：
2004-06-01
影响因子：
4.2
通讯作者：
Park, YM
中科院分区：
文献类型：
--
作者：
Hwang, YH;Choi, JY;Park, YM
全世界至少70%的肝细胞癌伴有肝硬化。为了探讨细胞凋亡和MAPK信号通路在肝癌发生中的作用，我们检测了肝硬化和肝癌中细胞凋亡和MAPK信号通路相关基因的表达谱。采用基因芯片、定量PCR和Western blot方法对67例肝硬化和33例肝癌患者的94份肝组织标本进行分析。在71个肝硬化相关基因中，c-raf-1和S6在28例肝硬化组织中分别有42.9%和32.1%表达上调，在五聚类K均值分析中，两个基因有很好的相关性。对于MAPK通路中的c-raf-1和下游基因，c-raf-1、MEK和MAPK在45例肝硬化标本中分别上调40%、80%和86.7%，在22例肝细胞癌标本中分别上调50%、63.6%和59.1%。Western印迹分析显示，91.2%（52/57）的肝硬化和100%（30/30）的肝细胞癌中激活的Raf-1过表达。26例配对标本中有14例（53.8%）Raf-1在肝细胞癌中的表达水平显著高于肝硬化（16.2 ± 20.3倍，P <0.05）。提示Raf-1的激活在肝癌的发生发展中起重要作用。(C)2004 Elsevier B.V.保留所有权利。
Liver cirrhosis accompanies at least 70% of hepatocellular carcinomas world-wide. To evaluate the dysregulation of apoptosis and the MAPK pathway in hepatocarcinogenesis, we investigated the expression profiles of the genes involved in apoptosis and MAPK pathway in cirrhosis and hepatocellular carcinoma. A total of 94 tissue specimens (61 cirrhosis and 33 hepatocellular carcinoma) obtained from 67 patients were analyzed by microarray, quantitative PCR and Western blot experiments. Of 71 apoptosis-associated genes, c-raf-1 and S6 were up-regulated in 42.9% and 32.1% of 28 cirrhosis tissues, respectively, and both genes were well correlated in a five-cluster K-means analysis. For c-raf-1 and down stream genes in the MAPK pathway, c-raf-1, MEK, and MAPK were up-regulated in 40%, 80%, and 86.7% of 45 cirrhosis specimens, respectively, and in 50%, 63.6%, and 59.1% of 22 hepatocellular carcinoma specimens, respectively. Western blot analysis showed that activated Raf-1 was over-expressed in 91.2% (52/57) of cirrhosis and in 100% (30/30) of hepatocellular carcinoma. The expression level of Raf-1 in 14 of 26 paired samples (53.8%) was significantly higher in hepatocellular carcinoma than in cirrhosis (16.2 +/- 20.3-fold, P < 0.05). These results suggest that the activation of Raf-1 plays an important role in the development of hepatocellular carcinoma. (C) 2004 Elsevier B.V. All rights reserved.