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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2002-1-4
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pubmed:abstractText |
Cyclooxygenase 2 plays a critical role in the development of gastrointestinal cancers in both human and animal models. About 80% of the gastric cancer showed a high level of expression of cyclooxygenase 2, but a subset of cases do not express without unknown reason. Aberrant methylation of CpG island of COX-2 was examined by using a series of gastric cancer cell lines and primary gastric cancers. Two out of 8 cell lines (25%) and 11 out of 93 (12%) primary cancers showed aberrant methylation of the 5' region of COX-2. Methylation of COX-2 was closely associated with loss of expression and treatment of methylation inhibitor, 5-deoxy-2'-azacytidine restored the expression of COX-2. A combined treatment of 5-deoxy-2'-azacytidine and a histone deacetylese inhibitor, trichostatin A, restored re-expression of the gene synergistically and chromatin immunoprecipitation analysis revealed that histone of methylated COX-2 promoter is deacetylated, indicating the role of cytosine methylation and histone deacetylation in the silencing of the gene. These results indicate that a subset of gastric cancer with COX-2 methylation evolves through the pathway that is independent of COX-2 expression and that COX-2 inhibitor may not be useful to induce apoptosis in these cases.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antimetabolites, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/Azacitidine,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cytosine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases,
http://linkedlifedata.com/resource/pubmed/chemical/Histones,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxamic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfites,
http://linkedlifedata.com/resource/pubmed/chemical/decitabine,
http://linkedlifedata.com/resource/pubmed/chemical/trichostatin A
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0020-7136
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2001 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
20
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pubmed:volume |
97
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
272-7
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11774276-Antimetabolites, Antineoplastic,
pubmed-meshheading:11774276-Apoptosis,
pubmed-meshheading:11774276-Azacitidine,
pubmed-meshheading:11774276-Cyclooxygenase 2,
pubmed-meshheading:11774276-Cytosine,
pubmed-meshheading:11774276-DNA,
pubmed-meshheading:11774276-DNA Methylation,
pubmed-meshheading:11774276-Enzyme Inhibitors,
pubmed-meshheading:11774276-Gastric Mucosa,
pubmed-meshheading:11774276-Gene Silencing,
pubmed-meshheading:11774276-Histone Deacetylases,
pubmed-meshheading:11774276-Histones,
pubmed-meshheading:11774276-Humans,
pubmed-meshheading:11774276-Hydroxamic Acids,
pubmed-meshheading:11774276-Immunohistochemistry,
pubmed-meshheading:11774276-Isoenzymes,
pubmed-meshheading:11774276-Membrane Proteins,
pubmed-meshheading:11774276-Methylation,
pubmed-meshheading:11774276-Polymorphism, Single-Stranded Conformational,
pubmed-meshheading:11774276-Precipitin Tests,
pubmed-meshheading:11774276-Promoter Regions, Genetic,
pubmed-meshheading:11774276-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:11774276-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:11774276-Stomach Neoplasms,
pubmed-meshheading:11774276-Sulfites,
pubmed-meshheading:11774276-Transcription, Genetic,
pubmed-meshheading:11774276-Tumor Cells, Cultured
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pubmed:year |
2002
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pubmed:articleTitle |
Aberrant methylation and histone deacetylation of cyclooxygenase 2 in gastric cancer.
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pubmed:affiliation |
First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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