Liver Cancer
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2005; 11(38): 5926-5930
Published online Oct 14, 2005. doi: 10.3748/wjg.v11.i38.5926
Overexpression of decoy receptor 3 in hepatocellular carcinoma and its association with resistance to Fas ligand-mediated apoptosis
Hong-Wei Shen, Shun-Liang Gao, Yu-Lian Wu, Shu-You Peng
Hong-Wei Shen, Shun-Liang Gao, Yu-Lian Wu, Shu-You Peng, Department of Surgery, 2nd Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310009, Zhejiang Province, China
Author contributions: All authors contributed equally to the work.
Correspondence to: Hong-Wei Shen, Department of Surgery, 2nd Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310009, Zhejiang Province, China. shenhongwei2002@yahoo.com
Telephone: +86-571-87783585 Fax: +86-571-87022776
Received: March 26, 2004
Revised: April 10, 2004
Accepted: April 13, 2004
Published online: October 14, 2005
Abstract

AIM: To characterize the expression and genomic amplification of decoy receptor 3 (DcR3) in hepatocellular carcinoma (HCC) and to evaluate the role of DcR3 in apoptosis.

METHODS: We examined 48 cases of HCC for DcR3 expression by RT-PCR and DcR3 gene amplification by quantitative genomic PCR. DcR3 protein was detected by immunohistochemistry. Terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick and labeling (TUNEL) was used to identify the apoptosis cells in tissues. Primary hepatoma cell culture and MTT test were used to evaluate the protection against FasL- and chemical-induced apoptosis by DcR3 expression.

RESULTS: DcR3 mRNA overexpression was detected in 60% HCC (29/48) patients. The occurrence of HCC was not associated with amplification of the gene. One sample base substitution was found in three sites as a sequence in Genbank. The expression of DcR3 in HCC was associated with the apoptotic index (0.067±0.04 vs 0.209±0.12, P<0.01), size of mass, stage, and infiltration or metastasis (41.2% vs 71.0%, 40% vs 75%, 51.8% vs 84.6%, P<0.05). DcR3 expression could protect hepatoma cells against apoptosis induced by FasL, but not by chemicals.

CONCLUSION: These data suggest that in addition to gene amplification there may be another mechanism underlying DcR3 overexpression. The effect of overexpression of DcR3 on the apoptosis of cancer cells may have direct therapeutic implications for the management of HCC.

Keywords: DcR3, Hepatocellular carcinoma, Apoptosis