title: Over-expression of c-raf-1 proto-oncogene in liver cirrhosis and hepatocellular carcinoma.
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 ( [Formula: see text] -fold, [Formula: see text] ). These results suggest that the activation of Raf-1 plays an important role in the development of hepatocellular carcinoma.
authors.affiliation: Hepatology Laboratory, Catholic Research Institute of Medical Science, Seoul, Republic of Korea.
authors.forename: Yeo Hyeon
authors.initials: YH
authors.lastname: Hwang
authors.forename: Jong Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Soyoun
authors.initials: S
authors.lastname: Kim
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Chung
authors.forename: Taeuk
authors.initials: T
authors.lastname: Kim
authors.forename: Sang Seok
authors.initials: SS
authors.lastname: Koh
authors.forename: Bogman
authors.initials: B
authors.lastname: Lee
authors.forename: Si Hyun
authors.initials: SH
authors.lastname: Bae
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.forename: Young Min
authors.initials: YM
authors.lastname: Park