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rdf:type |
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lifeskim:mentions |
umls-concept:C0012472,
umls-concept:C0021666,
umls-concept:C0086418,
umls-concept:C0140080,
umls-concept:C0220781,
umls-concept:C0699790,
umls-concept:C1515670,
umls-concept:C1518174,
umls-concept:C1565860,
umls-concept:C1704259,
umls-concept:C1705323,
umls-concept:C1705987,
umls-concept:C1883254
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pubmed:issue |
48
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pubmed:dateCreated |
2000-12-20
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pubmed:abstractText |
Nonsteroidal anti-inflammatory drugs reduce the risk of colon cancer and this effect is mediated in part through inhibition of type 2 prostaglandin endoperoxide synthase/ cyclo-oxygenase (COX-2). In the present study, we demonstrate that COX-2 expression and PGE2 synthesis are up-regulated by an IGF-II/IGF-I receptor autocrine pathway in Caco-2 colon carcinoma cells. COX-2 mRNA and PGE2 levels are higher in proliferating cells compared with post-confluent differentiated cells and in cells that constitutively overexpress IGF-II. Up-regulation of COX-2 expression by IGF-II is mediated through activation of IGF-I receptor because: (i) treatment of Caco-2 cells with a blocking antibody to the IGF-I receptor inhibits COX-2 mRNA expression; (ii) transfection of Caco-2 cells with a dominant negative IGF-I receptor reduces COX-2 expression and activity. Also, the blockade of the PI3-kinase, that mediates the proliferative effect of IGF-I receptor in Caco-2 cells, inhibits IGF-II-dependent COX-2 up-regulation and PGE2 synthesis. Moreover, COX-2 expression and activity inversely correlate with the increase of apoptosis in parental, IGF-II and dominant-negative IGF-I receptor transfected cells. This study suggests that induction of proliferation and tumor progression of colon cancer cells by the IGF-II/IGF-I receptor pathway may depend on the activation of COX-2-related events.
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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/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2 Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor II,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/N-(2-cyclohexyloxy-4-nitrophenyl)met...,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrobenzenes,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, IGF Type 1,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0950-9232
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5517-24
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11114729-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:11114729-Antibodies, Monoclonal,
pubmed-meshheading:11114729-Apoptosis,
pubmed-meshheading:11114729-Caco-2 Cells,
pubmed-meshheading:11114729-Cell Division,
pubmed-meshheading:11114729-Cyclooxygenase 2,
pubmed-meshheading:11114729-Cyclooxygenase 2 Inhibitors,
pubmed-meshheading:11114729-Cyclooxygenase Inhibitors,
pubmed-meshheading:11114729-Dinoprostone,
pubmed-meshheading:11114729-Disease Progression,
pubmed-meshheading:11114729-Humans,
pubmed-meshheading:11114729-Insulin-Like Growth Factor II,
pubmed-meshheading:11114729-Isoenzymes,
pubmed-meshheading:11114729-MAP Kinase Signaling System,
pubmed-meshheading:11114729-Membrane Proteins,
pubmed-meshheading:11114729-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:11114729-Nitrobenzenes,
pubmed-meshheading:11114729-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:11114729-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:11114729-RNA, Messenger,
pubmed-meshheading:11114729-Receptor, IGF Type 1,
pubmed-meshheading:11114729-Signal Transduction,
pubmed-meshheading:11114729-Sulfonamides,
pubmed-meshheading:11114729-Transfection,
pubmed-meshheading:11114729-Up-Regulation
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pubmed:year |
2000
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pubmed:articleTitle |
IGF-II/IGF-I receptor pathway up-regulates COX-2 mRNA expression and PGE2 synthesis in Caco-2 human colon carcinoma cells.
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pubmed:affiliation |
Dipartimento di Biologia e Patologia Cellulare e Molecolare, L Califano, Centro di Endocrinologia ed Oncologia Sperimentale G. Salvatore del Consiglio Nazionale delle Ricerche, Università Federico II, Napoli, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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