Overexpression of decoy receptor 3 in hepatocellular carcinoma and its association with resistance to Fas ligand-mediated apoptosis.
OBJECTIVE
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 sequence in Genbank. The expression of DcR3 in HCC was the associatied 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 be protect hepatoma cells against apoptosis induced by FasL, but not by chemicals.


CONCLUSIONS
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.
Shen
Hong-Wei
HW
Department of Surgery, 2(nd) Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310009, Zhejiang Province, China. shenhongwei2002@yahoo.com
Gao
Shun-Liang
SL
Wu
Yu-Lian
YL
Peng
Shu-You
SY
D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053222:Fas Ligand Protein; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000378:metabolism; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D048069:Tumor Necrosis Factors / Q000494:pharmacology
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C505911:TNFRSF6B protein, human; D048069:Tumor Necrosis Factors