Source:http://linkedlifedata.com/resource/pubmed/id/12941808
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
16
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pubmed:dateCreated |
2003-8-27
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pubmed:abstractText |
Membrane arachidonic acid is converted by cyclooxygenase (COX) into prostaglandin (PG) G(2) and then to PGH(2) which is subsequently metabolized to PGE(2) by PGE synthase (PGES). Both COX-1 and COX-2 play critical roles in intestinal polyp formation, whereas COX-2 is also expressed in cancers of a variety of organs. Likewise, inducible microsomal PGES (mPGES-1) is expressed in several types of cancer, although its role in benign polyp formation has not been investigated. We demonstrated recently that most COX-2-expressing cells in the polyps are stromal fibroblasts. Here we show colocalization of COX-1, COX-2 and mPGES in the intestinal polyp stromal fibroblasts of Apc(Delta 716) mice, a model for familial adenomatous polyposis. Contrary to COX-2 that was induced only in polyps >1 mm in diameter, COX-1 was found in polyps of any size. In polyps >1 mm, not only COX-2 but also mPGES was induced in the stromal fibroblasts where COX-1 had already been expressed. Although polyp number and size were markedly reduced in COX-1 (-/-) or COX-2 (-/-) compound mutant Apc mice, both COX-2 and mPGES were induced in the COX-1 (-/-) polyps, whereas COX-1 was expressed in the COX-2 (-/-) polyps. We found also in human familial adenomatous polyposis polyps that COX-2 and mPGES were induced in the COX-1-expressing fibroblasts. On the basis of these results, we propose that COX-1 expression in the stromal cells secures the basal level of PGE(2) that can support polyp growth to approximately 1 mm, and that simultaneous inductions of COX-2 and mPGES support the polyp expansion beyond approximately 1 mm by boosting the stromal PGE(2) production.
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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/Cyclooxygenase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Intramolecular Oxidoreductases,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/Ptgs1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/prostaglandin-E synthase
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
63
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4872-7
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12941808-Animals,
pubmed-meshheading:12941808-Cyclooxygenase 1,
pubmed-meshheading:12941808-Cyclooxygenase 2,
pubmed-meshheading:12941808-Enzyme Induction,
pubmed-meshheading:12941808-Intestinal Polyps,
pubmed-meshheading:12941808-Intramolecular Oxidoreductases,
pubmed-meshheading:12941808-Isoenzymes,
pubmed-meshheading:12941808-Membrane Proteins,
pubmed-meshheading:12941808-Mice,
pubmed-meshheading:12941808-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:12941808-Stromal Cells
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pubmed:year |
2003
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pubmed:articleTitle |
Cooperation of cyclooxygenase 1 and cyclooxygenase 2 in intestinal polyposis.
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pubmed:affiliation |
Department of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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