Different apoptotic regulation of TRAIL-caspase pathway in HBV- and HCV-related hepatocellular carcinoma.
Human hepatocellular carcinoma (HCC) appears to be strongly associated with apoptosis and its breakdown may be involved in the occurrence of HCC. Like the Fas/Fas-L system, the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) transduces apoptosis in a number of cancers; it is also a clinical candidate for cancer therapy. To examine its applicability in future therapy, the apoptotic pathway through TRAIL was investigated in HBV- and HCV-related HCC that have different mechanisms of hepatocarcinogenesis. Caspase-3 activity and the expression of four types of TRAIL receptor mRNAs were quantitated in tumor and contiguous non-tumor tissues obtained from 27 patients with HCC (HBV-related in 10; HCV-related in 17). The expression of caspase-3 and TRAIL receptors was also examined immunohistochemically. A significantly positive correlation was observed between caspase-3 activity and TRAIL-R1, -R2. Caspase-3 activity and TRAIL-R1, -R2 expression in tumor tissue were significantly lower than those in non-tumor tissue in HBV-related HCC. Some HCV-related HCC cases, however, demonstrated elevated caspase-3 activity and TRAIL-R1, -R2 expression in tumor tissue. HBV-related HCC demonstrated significantly suppressed caspase-3 activity, signifying apoptosis. Both TRAIL-R1 and -R2 showed coefficient correlation with caspase-3 activity, and were strongly associated with apoptosis in human HCC.
Yano
Yoshihiko
Y
Department of Clinical Molecular Medicine, Division of Diabetes, Digestive and Kidney Diseases, Kobe Asahi Hospital, Kobe, Japan.
Hayashi
Yoshitake
Y
Nakaji
Miyuki
M
Nagano
Hidenobu
H
Seo
Yasushi
Y
Ninomiya
Toshiaki
T
Yoon
Seitetsu
S
Wada
Atushi
A
Hirai
Midori
M
Kim
Soo Ryang
SR
Yokozaki
Hiroshi
H
Kasuga
Masato
M
D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D005260:Female; D006509:Hepatitis B / Q000378:metabolism; D006526:Hepatitis C / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases