Over-expression of c-raf-1 proto-oncogene in liver cirrhosis and hepatocellular carcinoma

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Title
Over-expression of c-raf-1 proto-oncogene in liver cirrhosis and hepatocellular carcinoma
Author(s)
Y H Hwang; J Y Choi; S Kim; E S Chung; T Kim; Sang Seok Koh; B Lee; S H Bae; J Kim; Y M Park
Bibliographic Citation
Hepatology Research, vol. 29, no. 2, pp. 113-121
Publication Year
2004
Abstract
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.
Keyword
hepatocarcinogenesishepatocellular carcinomaliver cirrhosisMAPK pathwayRaf-1ribosomal protein S6
ISSN
1386-6346
Publisher
Wiley
DOI
http://dx.doi.org/10.1016/j.hepres.2004.02.009
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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