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rdf:type |
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lifeskim:mentions |
umls-concept:C0014597,
umls-concept:C0017262,
umls-concept:C0040624,
umls-concept:C0185117,
umls-concept:C0521362,
umls-concept:C0812246,
umls-concept:C1414313,
umls-concept:C1456820,
umls-concept:C1565860,
umls-concept:C1705323,
umls-concept:C2911684
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pubmed:issue |
2
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pubmed:dateCreated |
2011-7-28
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pubmed:abstractText |
TNF and epidermal growth factor (EGF) are well-known stimuli of cyclooxygenase (COX)-2 expression, and TNF stimulates transactivation of EGF receptor (EGFR) signaling to promote survival in colon epithelial cells. We hypothesized that COX-2 induction and cell survival signaling downstream of TNF are mediated by EGFR transactivation. TNF treatment was more cytotoxic to COX-2(-/-) mouse colon epithelial (MCE) cells than wild-type (WT) young adult mouse colon (YAMC) epithelial cells or COX-1(-/-) cells. TNF also induced COX-2 protein and mRNA expression in YAMC cells, but blockade of EGFR kinase activity or expression inhibited COX-2 upregulation. TNF-induced COX-2 expression was reduced and absent in EGFR(-/-) and TNF receptor-1 (TNFR1) knockout MCE cells, respectively, but was restored upon expression of the WT receptors. Inhibition of mediators of EGFR transactivation, Src family kinases and p38 MAPK, blocked TNF-induced COX-2 protein and mRNA expression. Finally, TNF injection increased COX-2 expression in colon epithelium of WT, but not kinase-defective EGFR(wa2) and EGFR(wa5), mice. These data indicate that TNFR1-dependent transactivation of EGFR through a p38- and/or an Src-dependent mechanism stimulates COX-2 expression to promote cell survival. This highlights an EGFR-dependent cell signaling pathway and response that may be significant in colitis-associated carcinoma.
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pubmed:grant |
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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/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1522-1547
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
301
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
G220-9
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pubmed:meshHeading |
pubmed-meshheading:21566012-Animals,
pubmed-meshheading:21566012-Cell Line,
pubmed-meshheading:21566012-Cell Survival,
pubmed-meshheading:21566012-Colon,
pubmed-meshheading:21566012-Cyclooxygenase 2,
pubmed-meshheading:21566012-Epithelial Cells,
pubmed-meshheading:21566012-Gene Expression Regulation,
pubmed-meshheading:21566012-Mice,
pubmed-meshheading:21566012-Mice, Inbred C57BL,
pubmed-meshheading:21566012-Mice, Knockout,
pubmed-meshheading:21566012-RNA, Messenger,
pubmed-meshheading:21566012-RNA, Small Interfering,
pubmed-meshheading:21566012-Receptor, Epidermal Growth Factor,
pubmed-meshheading:21566012-Receptors, Tumor Necrosis Factor, Type I,
pubmed-meshheading:21566012-Signal Transduction,
pubmed-meshheading:21566012-Stomach,
pubmed-meshheading:21566012-Transcriptional Activation,
pubmed-meshheading:21566012-Transfection,
pubmed-meshheading:21566012-Tumor Necrosis Factor-alpha,
pubmed-meshheading:21566012-p38 Mitogen-Activated Protein Kinases,
pubmed-meshheading:21566012-src-Family Kinases
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pubmed:year |
2011
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pubmed:articleTitle |
TNF transactivation of EGFR stimulates cytoprotective COX-2 expression in gastrointestinal epithelial cells.
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pubmed:affiliation |
Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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