| The purpose of this study was designed to investigate the possible mechanism of HCC using a rat model induced by a chemical carcinogen DENA. Both HCC and normal liver tissue samples were employed for microarray and proteomics. Using 2D-DIGE and matrix-assisted laser desorption/ionization time-of-flight MS, we identified 18 spots corresponding to differentially expressed proteins in the liver of rat hepatoma induced by diethylnitrosamine. Among these tumor-associated variants, the most prominent up-regulated proteins included members of the glutathione S-transferases (GST) super-family, aldo-keto reductase superfamily and proteins involved in the response to oxidative stress. The decreased abundance was observed for fumarylacetoacetase, a protein with high incidence of hepatocellular carcinoma; and for 3-oxo-5-beta-steroid 4-dehydrogenase, an enzyme in deficiency may contribute to hepatic dysfunction. In addition, the dermcidin, a sweat-specific protein, was found in the tissue of rat hepatoma. Moreover, the corresponding samples were assessed by Agilent microarray analysis to show changes in transcript levels. To confirm the proteomic findings further, western blot analysis and histological immunostaining were employed. For microarray analysis of the same samples, bioinformatic analysis revealed that 789 were up-regulated and 559 gene were down-regulated significantly, of which some deregulated genes significantly would be the markers for HCC induced by the chemical carcinogen. Further studies should be performed to confirm this result. As the HCC model has the similarity to human HCC, these data have important implications in understanding the mechanism of HCC. In summary, our results demonstrated that the combination of proteomic and genomic analyses will aid in determining tumor-associated protein variants and in understanding the mechanism of tumorgenesis.
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