Document Detail


Expression of TNF-related apoptosis-inducing ligand in human hepatocellular carcinoma.
MedLine Citation:
PMID:  15809718     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
TNF-related apoptosis-inducing ligand (TRAIL), as well as Fas ligand, plays a pivotal role in lymphocyte cytotoxicity and the maintenance of immunological homeostasis in various tissues, but its physiological role in immune evasion of cancer cells remains unknown. We have previously shown strong resistance to TRAIL-induced cytotoxicity in human hepatocellular carcinomas (HCCs). The current study investigates the expression of TRAIL in HCCs. We found that three HCC cells, HepG2, Hep3B and Huh7 cells, constitutively express TRAIL mRNA and protein, as detected by reverse transcriptase PCR and Western blotting. Four of 10 human HCC tissues demonstrated positive staining for TRAIL, whereas non-tumor tissues showed little detectable staining. TRAIL expression on tumor cells was detected by flow cytometry and was dramatically induced after the addition of doxorubicin, a chemotherapeutic agent, or cytokine stimulation with TNF-alpha, IL-1beta or IL-18. This expression was induced principally via the NF-kappaB activation pathway, since IkappaB transfection significantly reduced TRAIL expression. In addition, the expressed TRAIL was functional. The TRAIL on HCC cells induced apoptosis in Jurkat cells that are sensitive to TRAIL-mediated apoptosis, and this process was specifically inhibited by recombinant TRAIL-receptors:Fc which binds to TRAIL. In conclusion, TRAIL expressed on the surface of HCC cells by cytokines or cytostatic drugs might contribute to an alternative mechanism that enables tumors to evade immune surveillance by inducing apoptosis of activated human lymphocytes.
Authors:
Katsuya Shiraki; Takenari Yamanaka; Hidekazu Inoue; Tomoyuki Kawakita; Naoyuki Enokimura; Hiroshi Okano; Kazushi Sugimoto; Kazumoto Murata; Takeshi Nakano
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of oncology     Volume:  26     ISSN:  1019-6439     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-05     Completed Date:  2005-07-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1273-81     Citation Subset:  IM    
Affiliation:
First Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie 514-8507, Japan. katsuyas@clin.medic.mie-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Antibiotics, Antineoplastic / pharmacology
Antigens, CD95
Apoptosis*
Apoptosis Regulatory Proteins
Carcinoma, Hepatocellular / genetics*,  pathology
Doxorubicin / pharmacology
Flow Cytometry
Gene Expression Profiling*
Humans
Jurkat Cells
Ligands
Liver Neoplasms / genetics*,  pathology
Lymphocytes
Membrane Glycoproteins / biosynthesis*
NF-kappa B / metabolism
Receptors, Tumor Necrosis Factor / metabolism
Reverse Transcriptase Polymerase Chain Reaction
TNF-Related Apoptosis-Inducing Ligand
Transfection
Tumor Necrosis Factor-alpha / biosynthesis*
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Antigens, CD95; 0/Apoptosis Regulatory Proteins; 0/Ligands; 0/Membrane Glycoproteins; 0/NF-kappa B; 0/Receptors, Tumor Necrosis Factor; 0/TNF-Related Apoptosis-Inducing Ligand; 0/TNFSF10 protein, human; 0/Tumor Necrosis Factor-alpha; 23214-92-8/Doxorubicin

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