Source:http://linkedlifedata.com/resource/pubmed/id/15531912
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2005-1-7
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pubmed:abstractText |
Evidence exists that alterations of the genes encoding apoptosis-related proteins contribute to either development or progression of human cancers. Caspase-8 plays a crucial role in the initiation phase of apoptosis. To explore the possibility that the genetic alteration of caspase-8 gene is involved in the development of hepatocellular carcinomas (HCCs), we have analysed the entire coding region of human caspase-8 gene for the detection of somatic mutations by polymerase chain reaction-single-strand conformation polymorphism in 69 HCCs with low-grade dysplastic nodule (LGDN, n=2) or high-grade dysplastic nodule (HGDN, n=2) or without any dysplastic nodules (n=65). Overall, we detected a total of nine somatic mutations in 69 HCCs (13.0%). Interestingly, all of the nine mutations were an identical frameshift mutation with two base-pair deletion (1225_1226delTG), which would result in a premature termination of amino-acid synthesis in the p10 protease subunit. In a patient sample, we detected the 1225_1226delTG mutation both in HCC and LDGN lesions, suggesting that caspase-8 mutation could be involved in the early stage of HCC carcinogenesis. We expressed the tumor-derived caspase-8 mutant in the cells and found that the mutant abolished cell death activity of caspase-8. Our data indicate that caspase-8 gene is frequently mutated in HCC and the majority of the mutations may be the frameshift mutation 1225_1226delTG. Also, the data suggest that caspase-8 gene mutation might lead to the loss of its cell death function and contribute to the pathogenesis of HCC.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/FADD protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fas-Associated Death Domain Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0950-9232
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
24
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
141-7
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15531912-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:15531912-Alleles,
pubmed-meshheading:15531912-Apoptosis,
pubmed-meshheading:15531912-Carcinoma, Hepatocellular,
pubmed-meshheading:15531912-Caspase 8,
pubmed-meshheading:15531912-Caspases,
pubmed-meshheading:15531912-Fas-Associated Death Domain Protein,
pubmed-meshheading:15531912-Frameshift Mutation,
pubmed-meshheading:15531912-Humans,
pubmed-meshheading:15531912-Immunohistochemistry,
pubmed-meshheading:15531912-Liver Neoplasms,
pubmed-meshheading:15531912-Organ Specificity,
pubmed-meshheading:15531912-Protein Binding
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pubmed:year |
2005
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pubmed:articleTitle |
Caspase-8 gene is frequently inactivated by the frameshift somatic mutation 1225_1226delTG in hepatocellular carcinomas.
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pubmed:affiliation |
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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