Source:http://linkedlifedata.com/resource/pubmed/id/16575786
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2006-4-10
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pubmed:abstractText |
The death-associated protein kinase (DAP-kinase) is a cytoskeleton-associated protein crucially involved in the induction of early apoptotic pathways. Aberrant hypermethylation of the DAP-kinase promoter plays a major role in tumorigenesis. We aimed to investigate the inactivation of DAP-kinase and its association with apoptotic cell death in 94 colorectal carcinomas. DAP-kinase promoter hypermethylation and mRNA expression were investigated using methylation-specific PCR and real-time RT-PCR, respectively. The expression of DAP-kinase, Fas, and Fas-ligand (FasL) proteins was studied by immunohistochemistry and immunofluorescence. Apoptosis of tumour cells was investigated using the TUNEL assay. DAP-kinase was expressed in tumour cells and tumour-invading macrophages and was closely associated with high numbers of apoptotic tumour cells. DAP-kinase expression co-localized with FasL overexpression in tumour-associated macrophages, and aberrant promoter hypermethylation was verified in more than 50% of carcinomas. There was a tendency for proximal tumours to show DAP-kinase promoter methylation more frequently (p = 0.07). Promoter methylation resulted in a decrease or loss of DAP-kinase protein expression in tumour cells and tumour-associated macrophages. Simultaneously, a decreased apoptotic count and loss of Fas/FasL expression was observed in tumour cells. Our study is the first to demonstrate DAP-kinase expression in invading tumour-associated macrophages in colorectal cancer. The presence of similar expression levels of DAP-kinase in tumour cells and associated macrophages, and their dependence on the promoter methylation status of the tumour cells, suggests cross talk between these cell types during apoptotic cell death.
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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/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/FASLG protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fas Ligand Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factors,
http://linkedlifedata.com/resource/pubmed/chemical/death-associated protein kinase
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-3417
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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pubmed:issnType |
Print
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pubmed:volume |
209
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
95-105
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:16575786-Aged,
pubmed-meshheading:16575786-Apoptosis,
pubmed-meshheading:16575786-Apoptosis Regulatory Proteins,
pubmed-meshheading:16575786-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:16575786-Colorectal Neoplasms,
pubmed-meshheading:16575786-DNA Methylation,
pubmed-meshheading:16575786-Fas Ligand Protein,
pubmed-meshheading:16575786-Female,
pubmed-meshheading:16575786-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:16575786-Humans,
pubmed-meshheading:16575786-In Situ Nick-End Labeling,
pubmed-meshheading:16575786-Macrophages,
pubmed-meshheading:16575786-Male,
pubmed-meshheading:16575786-Membrane Glycoproteins,
pubmed-meshheading:16575786-Microsatellite Repeats,
pubmed-meshheading:16575786-Middle Aged,
pubmed-meshheading:16575786-Neoplasm Staging,
pubmed-meshheading:16575786-Polymerase Chain Reaction,
pubmed-meshheading:16575786-Promoter Regions, Genetic,
pubmed-meshheading:16575786-RNA, Messenger,
pubmed-meshheading:16575786-RNA, Neoplasm,
pubmed-meshheading:16575786-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16575786-Tumor Necrosis Factors
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pubmed:year |
2006
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pubmed:articleTitle |
Close localization of DAP-kinase positive tumour-associated macrophages and apoptotic colorectal cancer cells.
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pubmed:affiliation |
Department of Pathology, Otto-von-Guericke University Magdeburg, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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