Proteomic analysis of liver tissue from HBx-transgenic mice at early stages of hepatocarcinogenesis.
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.
Kim
Sun-Young
SY
Medical Proteomics Research Center, KRIBB, 52 Eoeun-Dong, Yusung-Gu, Daejeon, South Korea.
Lee
Phil Young
PY
Shin
Hye-Jun
HJ
Kim
Do Hyung
DH
Kang
Sunghyun
S
Moon
Hyung-Bae
HB
Kang
Sang Won
SW
Kim
Jin-Man
JM
Park
Sung Goo
SG
Park
Byoung Chul
BC
Yu
Dae-Yeul
DY
Bae
Kwang-Hee
KH
Lee
Sang Chul
SC
D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D002853:Chromatography, Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D015972:Gene Expression Regulation, Neoplastic; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D040901:Proteomics; D053719:Tandem Mass Spectrometry; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein