Proteomic identification of down-regulation of oncoprotein DJ-1 and proteasome activator subunit 1 in hepatitis B virus-infected well-differentiated hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is a common malignant tumour. Development of HCC is a multi-step process from well-differentiated (G1), moderately differentiated (G2) to poorly differentiated (G3) phenotype. The early molecular modulators causing the onset of hepatocarcinogenesis are not fully understood. In the present study, we conducted comparative proteomics to analyze the differential proteome of G1 tumour and adjacent non-tumour tissues, with aims to identify the molecules as early tumour markers and to understand the early molecular events involved in initiation of tumorigenesis in hepatitis B virus (HBV)-infected G1 tumour. Differentially expressed proteins were identified by MALDI-TOF/TOF tandem mass spectrometry and NCBInr database interrogation. A total of 15 differentially expressed proteins with diverse biological functions were identified. Among these, 4 proteins were down-regulated, whereas the other 11 proteins were up-regulated in the G1 tumours. Two proteins, Proteasome activator subunit 1 (PA28alpha) and DJ-1, were firstly found to be down-regulated in HBV-infected G1 tumours. Down-regulations of these two proteins were further validated by Western blotting and immunohistochemistry in a panel of clinical specimens. These findings elucidate, at least in part, the molecular events underlying the mechanism and the potential roles of DJ-1 and PA28alpha in the onset of hepatocarcinogenesis.
Molecular Diagnosis Centre, Department of Laboratory Medicine, National University Hospital, Singapore. daohai_zhang@nuh.com.sg
Daohai
D
Zhang
Seng Gee
SG
Lim
Evelyn S C
ES
Koay
D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006515:Hepatitis B virus / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009124:Muscle Proteins / Q000096:biosynthesis*; D015513:Oncogene Proteins / Q000096:biosynthesis*; D046988:Proteasome Endopeptidase Complex / Q000096:biosynthesis*; D000071617:Protein Deglycase DJ-1; D040901:Proteomics / Q000379:methods*; D016622:Silver Staining; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D015513:Oncogene Proteins; C085047:PSME1 protein, human; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D046988:Proteasome Endopeptidase Complex