rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
2003-4-7
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pubmed:abstractText |
Although epidemiological studies have long established that inorganic arsenic is a potent human carcinogen, the underlying mechanisms are still poorly understood. Recent studies suggest that inorganic arsenic may act as a tumor promoter by perturbing key signaling transduction pathways. We have shown previously that arsenite can potently activate the mitogen-activated protein kinase cascades and induce the expression of proliferation-associated genes, including proto-oncogenes c-jun and c-fos. In order to elucidate further the molecular mechanisms underlying its tumor-promoting properties, we investigated the signaling events involved in arsenite-mediated induction of c-fos and c-jun. We found that induction of both c-fos and c-jun by arsenite can be substantially inhibited by the MEK- selective inhibitor U0126, suggesting that the ERK pathway is critically involved in their up-regulation. Interestingly, arsenite dramatically induced the phosphorylation and acetylation of histone H3 preceding the induction of mRNAs encoding c-fos and c-jun. Finally, chromatin immunoprecipitation assays revealed that arsenite treatment markedly induced the phosphorylation/acetylation of histone H3 associated with the c-fos and c-jun genes through an ERK-dependent pathway. Our results strongly suggest that arsenic-triggered alterations in chromatin structure perturb specific gene transcription, including that of proto-oncogenes c-jun and c-fos, and may thereby contribute to the carcinogenic process.
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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/Arsenites,
http://linkedlifedata.com/resource/pubmed/chemical/Butadienes,
http://linkedlifedata.com/resource/pubmed/chemical/Carcinogens,
http://linkedlifedata.com/resource/pubmed/chemical/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Histones,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Nitriles,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoserine,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Protein S6 Kinases, 90-kDa,
http://linkedlifedata.com/resource/pubmed/chemical/U 0126,
http://linkedlifedata.com/resource/pubmed/chemical/arsenite,
http://linkedlifedata.com/resource/pubmed/chemical/mitogen and stress-activated...,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
13183-91
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12547826-Acetylation,
pubmed-meshheading:12547826-Arsenites,
pubmed-meshheading:12547826-Base Sequence,
pubmed-meshheading:12547826-Butadienes,
pubmed-meshheading:12547826-Carcinogens,
pubmed-meshheading:12547826-Cell Cycle,
pubmed-meshheading:12547826-Chromatin,
pubmed-meshheading:12547826-DNA Primers,
pubmed-meshheading:12547826-Diploidy,
pubmed-meshheading:12547826-Enzyme Inhibitors,
pubmed-meshheading:12547826-Fibroblasts,
pubmed-meshheading:12547826-Genes, fos,
pubmed-meshheading:12547826-Genes, jun,
pubmed-meshheading:12547826-Histones,
pubmed-meshheading:12547826-Humans,
pubmed-meshheading:12547826-Kinetics,
pubmed-meshheading:12547826-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12547826-Nitriles,
pubmed-meshheading:12547826-Phosphorylation,
pubmed-meshheading:12547826-Phosphoserine,
pubmed-meshheading:12547826-Polymerase Chain Reaction,
pubmed-meshheading:12547826-RNA, Messenger,
pubmed-meshheading:12547826-Ribosomal Protein S6 Kinases, 90-kDa,
pubmed-meshheading:12547826-Transcription, Genetic,
pubmed-meshheading:12547826-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2003
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pubmed:articleTitle |
Tumor promoter arsenite stimulates histone H3 phosphoacetylation of proto-oncogenes c-fos and c-jun chromatin in human diploid fibroblasts.
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pubmed:affiliation |
Laboratory of Cellular and Molecular Biology, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA.
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pubmed:publicationType |
Journal Article
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