Enhanced nuclear factor-kappa B-associated Wnt-1 expression in hepatitis B- and C-related hepatocarcinogenesis: identification by functional proteomics.
Chronic infections with hepatitis B and C viruses (HBV and HCV) are etiologically linked to hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Both viruses may induce activation of nuclear factor-kappa B (NF-kappaB) in hepatocytes that plays a crucial role in the regulation of cell growth and apoptosis. Functional proteomics analysis of proteins associated with NF-kappaB signaling complexes in both viruses-related HCC tumor and non-tumor tissues may disclose possible common mechanisms in hepatocarcinogenesis. By functional proteomics, we analyzed proteins associated with NF-kappaB-signaling complexes in four-paired human HCC tumor and non-tumor tissues from HBV- and HCV-infected patients, respectively, and in one-paired tissue with dual viral infection. The quantity of NF-kappaB-associated proteins was semi-quantitatively measured by protein spot intensity on the gels of two-dimensional polyacrylamide gel electrophoresis. The results showed that overexpression of NF-kappaB-associated Wnt-1 protein in tumor part was detected in the majority of HBV- and HCV-infected HCC samples. These data suggest that enhanced expression of NF-kappaB-associated Wnt-1 protein might be a mechanism of hepatocarcinogenesis common to HBV- and HCV-infected patients. NF-kappaB signaling pathway and Wnt-1 protein could be potential targets for designing highly effective therapeutic agents in treating HCC and for chemoprevention of hepatocarcinogenesis.
Lee
Tzong-Hsien
TH
Liver Research Unit, Chang-Gung Memorial Hospital, Linko, Taiwan.
Tai
Dar-In
DI
Cheng
Cha-Ju
CJ
Sun
Chi-Shu
CS
Lin
Ching-Yih
CY
Sheu
Ming-Jen
MJ
Lee
Wei-Ping
WP
Peng
Cheng-Yuan
CY
Wang
Andrew H-J
AH
Tsai
Sun-Lung
SL
D000368:Aged; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D016174:Hepacivirus / Q000378:metabolism; D006509:Hepatitis B / Q000150:complications* / Q000378:metabolism; D006515:Hepatitis B virus / Q000378:metabolism; D006526:Hepatitis C / Q000150:complications* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000209:etiology / Q000378:metabolism / Q000821:virology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D015398:Signal Transduction / Q000502:physiology; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism*
D016328:NF-kappa B; D009363:Neoplasm Proteins; D010455:Peptides; D051155:Wnt1 Protein