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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2006-2-20
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pubmed:abstractText |
Cyclooxygenase-2 (COX-2) expression is a marker of poor prognosis in gastric cancer patients, and its inhibition suppresses gastric tumorigenesis in experimental animal models. The mechanism that leads to COX-2 overexpression in this tumor type is unknown. We have now shown that inhibition of phosphatidylinositol 3-kinase by LY294002 suppresses both basal and phorbol myristate acetate-induced COX-2 expression in TMK-1 and MKN-28 gastric cancer cells. Furthermore, inhibition of glycogen synthase kinase-3beta (GSK-3beta) by SB415286 induced expression of COX-2 mRNA and protein as well as the enzyme activity in the gastric cancer cells. The effect of SB415286 was confirmed by the use of two additional GSK-3beta inhibitors, lithium chloride and SB216763. SB415286 had a modest 1.6-fold stimulatory effect on a 2-kb COX-2 promoter reporter construct, but more importantly, it was shown to block the decay of COX-2 mRNA. In contrast to modulation of phosphatidylinositol 3-kinase/Akt/GSK-3beta pathway, inhibitors of mitogen-activated protein kinases (MEK 1/2, p38, JNK) or the mammalian target of rapamycin did not alter COX-2 expression in gastric cancer cells. Our data show that inhibition of GSK-3beta stimulates COX-2 expression in gastric cancer cells, which seems to be primarily facilitated via an increase in mRNA stability and to a lesser extent through enhanced transcription.
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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/2-(4-morpholinyl)-8-phenyl-4H-1-benz...,
http://linkedlifedata.com/resource/pubmed/chemical/3-(3-chloro-4-hydroxyphenylamino)-4-...,
http://linkedlifedata.com/resource/pubmed/chemical/Aminophenols,
http://linkedlifedata.com/resource/pubmed/chemical/Chromones,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Lithium Chloride,
http://linkedlifedata.com/resource/pubmed/chemical/Maleimides,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/SB 216763,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
281
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4564-9
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:16371352-Aminophenols,
pubmed-meshheading:16371352-Blotting, Northern,
pubmed-meshheading:16371352-Blotting, Western,
pubmed-meshheading:16371352-Cell Line, Tumor,
pubmed-meshheading:16371352-Chromones,
pubmed-meshheading:16371352-Cyclooxygenase 2,
pubmed-meshheading:16371352-Dinoprostone,
pubmed-meshheading:16371352-Enzyme Inhibitors,
pubmed-meshheading:16371352-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:16371352-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:16371352-Genes, Reporter,
pubmed-meshheading:16371352-Glycogen Synthase Kinase 3,
pubmed-meshheading:16371352-Humans,
pubmed-meshheading:16371352-Indoles,
pubmed-meshheading:16371352-Lithium Chloride,
pubmed-meshheading:16371352-Maleimides,
pubmed-meshheading:16371352-Models, Biological,
pubmed-meshheading:16371352-Models, Statistical,
pubmed-meshheading:16371352-Morpholines,
pubmed-meshheading:16371352-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:16371352-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:16371352-RNA,
pubmed-meshheading:16371352-RNA, Messenger,
pubmed-meshheading:16371352-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16371352-Signal Transduction,
pubmed-meshheading:16371352-Stomach Neoplasms,
pubmed-meshheading:16371352-Tetradecanoylphorbol Acetate,
pubmed-meshheading:16371352-Time Factors,
pubmed-meshheading:16371352-Transfection
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pubmed:year |
2006
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pubmed:articleTitle |
Expression of cyclooxygenase-2 is regulated by glycogen synthase kinase-3beta in gastric cancer cells.
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pubmed:affiliation |
Department of Pathology, Helsinki University Central Hospital, and Molecular and Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki, 00014 Helsinki, Finland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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