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Proteomic analysis of liver tissue from HBx-transgenic mice at early stages of hepatocarcinogenesis.

Abstract
The hepatitis B virus X-protein (HBx), a multifunctional viral regulator, participates in the viral life cycle and in the development of hepatocellular carcinoma (HCC). We previously reported a high incidence of HCC in transgenic mice expressing HBx. In this study, proteomic analysis was performed to identify proteins that may be involved in hepatocarcinogenesis and/or that could be utilized as early detection biomarkers for HCC. Proteins from the liver tissue of HBx-transgenic mice at early stages of carcinogenesis (dysplasia and hepatocellular adenoma) were separated by 2-DE, and quantitative changes were analyzed. A total of 22 spots displaying significant quantitative changes were identified using LC-MS/MS. In particular, several proteins involved in glucose and fatty acid metabolism, such as mitochondrial 3-ketoacyl-CoA thiolase, intestinal fatty acid-binding protein 2 and cytoplasmic malate dehydrogenase, were differentially expressed, implying that significant metabolic alterations occurred during the early stages of hepatocarcinogenesis. The results of this proteomic analysis provide insights into the mechanism of HBx-mediated hepatocarcinogenesis. Additionally, this study identifies possible therapeutic targets for HCC diagnosis and novel drug development for treatment of the disease.
AuthorsSun-Young Kim, Phil Young Lee, Hye-Jun Shin, Do Hyung Kim, Sunghyun Kang, Hyung-Bae Moon, Sang Won Kang, Jin-Man Kim, Sung Goo Park, Byoung Chul Park, Dae-Yeul Yu, Kwang-Hee Bae, Sang Chul Lee
JournalProteomics (Proteomics) Vol. 9 Issue 22 Pg. 5056-66 (Nov 2009) ISSN: 1615-9861 [Electronic] Germany
PMID19813210 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein
Topics
  • Animals
  • Blotting, Western
  • Carcinoma, Hepatocellular (genetics, metabolism)
  • Chromatography, Liquid
  • Electrophoresis, Gel, Two-Dimensional
  • Gene Expression Regulation, Neoplastic
  • Liver (metabolism, pathology)
  • Mice
  • Mice, Transgenic
  • Polymerase Chain Reaction
  • Proteomics
  • Tandem Mass Spectrometry
  • Trans-Activators (genetics, metabolism)
  • Viral Regulatory and Accessory Proteins

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