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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2007-3-30
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pubmed:abstractText |
Activation of the signaling pathways leading to gene expression regulation is critical in the carcinogenic effects of nickel exposure. In the present study, we found nickel exposure could induce cyclooxygenase-2 (COX-2) expression at transcriptional and protein levels in both human bronchoepithelial cells (Beas-2B) and murine embryonic fibroblasts (MEFs). We further provided direct evidence for the specific involvement of the JNK1 signaling pathway in the COX-2 induction using specific gene knockout approaches. Our results demonstrated that COX-2 induction by nickel was impaired in JNK1(-/-) MEFs, but not in JNK2(-/-) MEFs. Moreover, re-constitutional expression of JNK1 restored COX-2 induction, confirming the specific requirement of JNK1 in COX-2 induction. Further investigation revealed that JNK1 mediated the nickel-induced COX-2 expression in a c-Jun/AP-1-dependent manner. Ectopic expression of TAM67, a c-Jun dominant negative mutant, also suppressed the COX-2 induction. Our results demonstrate that the JNK1/c-Jun/AP-1 pathway, but not the JNK2 pathway, plays a critical role in nickel-induced COX-2 expression.
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0143-3334
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
28
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
883-91
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17065197-Animals,
pubmed-meshheading:17065197-Blotting, Western,
pubmed-meshheading:17065197-Bronchi,
pubmed-meshheading:17065197-Cells, Cultured,
pubmed-meshheading:17065197-Cyclooxygenase 2,
pubmed-meshheading:17065197-Embryo, Mammalian,
pubmed-meshheading:17065197-Enzyme Activation,
pubmed-meshheading:17065197-Epithelial Cells,
pubmed-meshheading:17065197-Fibroblasts,
pubmed-meshheading:17065197-Homozygote,
pubmed-meshheading:17065197-Humans,
pubmed-meshheading:17065197-Membrane Proteins,
pubmed-meshheading:17065197-Mice,
pubmed-meshheading:17065197-Mice, Knockout,
pubmed-meshheading:17065197-Mitogen-Activated Protein Kinase 8,
pubmed-meshheading:17065197-Mitogen-Activated Protein Kinase 9,
pubmed-meshheading:17065197-Nickel,
pubmed-meshheading:17065197-Respiratory Mucosa,
pubmed-meshheading:17065197-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:17065197-Signal Transduction
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pubmed:year |
2007
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pubmed:articleTitle |
JNK1, but not JNK2, is required for COX-2 induction by nickel compounds.
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pubmed:affiliation |
Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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