Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2003-4-7
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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...
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13183-91
pubmed:dateRevised
2009-11-19
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
pubmed:year
2003
pubmed:articleTitle
Tumor promoter arsenite stimulates histone H3 phosphoacetylation of proto-oncogenes c-fos and c-jun chromatin in human diploid fibroblasts.
pubmed:affiliation
Laboratory of Cellular and Molecular Biology, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA.
pubmed:publicationType
Journal Article