Document Detail


Alterations of Fas-pathway genes associated with nodal metastasis in non-small cell lung cancer.
MedLine Citation:
PMID:  12037669     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Many types of cancer cells are resistant to Fas-mediated apoptosis by several mechanisms, including the mutations of the genes involved in Fas-mediated apoptosis. In this study, to explore the possibility that the mutations of the genes involved in the proximal pathway of Fas-mediated apoptosis (Fas, FADD, caspase 8 and caspase 10) are involved in cancer metastasis, we have analysed somatic mutation and deletion of these genes in 80 non-small cell lung cancers (NSCLCs) with (n=43) and without (n=37) metastasis to the regional lymph nodes. We found 12 mutations (four Fas, four FADD, and four caspase 10 mutations) in 11 of 80 NSCLCs (13.8%). Interestingly, of these mutations, most mutations (10 out of 12) were detected in the NSCLCs with metastasis, and the frequency in the metastasis lesions (23%) was higher than that in the primary lesions of the NSCLCs without metastasis (5.4%). Furthermore, transfection study revealed that the tumor-derived mutants have decreased apoptosis inductions compared to the wild types. These data suggest that the inactivating mutations of the genes in the proximal pathway of Fas-mediated apoptosis may lead to a decreased cancer cell death and play a role in the metastasis of NSCLC.
Authors:
Min Sun Shin; Hong Sug Kim; Sug Hyung Lee; Jong Woo Lee; Young Hwa Song; Young Sill Kim; Won Sang Park; Su Young Kim; Shi Nae Lee; Jik Young Park; Jong Heun Lee; Wensua Xiao; Keon Hyon Jo; Young Pil Wang; Kyo Young Lee; Yong Gyu Park; Sang Ho Kim; Jung Young Lee; Nam Jin Yoo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncogene     Volume:  21     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-05-30     Completed Date:  2002-07-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  4129-36     Citation Subset:  IM    
Affiliation:
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing*
Alleles
Antigens, CD95 / genetics*
Apoptosis / genetics
Base Sequence
Carcinoma, Non-Small-Cell Lung / genetics*,  pathology
Carrier Proteins / genetics*
Caspase 10
Caspase 8
Caspase 9
Caspases / genetics*
DNA Primers
Fas-Associated Death Domain Protein
Humans
Loss of Heterozygosity
Lung Neoplasms / genetics*,  pathology
Lymphatic Metastasis / genetics*
Mutagenesis, Site-Directed
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Antigens, CD95; 0/CASP10 protein, human; 0/Carrier Proteins; 0/DNA Primers; 0/FADD protein, human; 0/Fas-Associated Death Domain Protein; EC 3.4.22.-/CASP8 protein, human; EC 3.4.22.-/CASP9 protein, human; EC 3.4.22.-/Caspase 10; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Caspases

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