Source:http://linkedlifedata.com/resource/pubmed/id/18271921
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2008-2-14
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pubmed:abstractText |
Epidermal growth factor receptor (EGFR) gene alterations have been found in human lung cancers. However, there is no information on the factors inducing EGFR mutations. In rodents, K-ras mutations are frequently found in many lung carcinogenesis models, but hitherto, Egfr mutations have not been reported. Their presence was therefore investigated in representative lung carcinogenesis models with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosobis(2-hydroxypropyl)amine (BHP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and ethyl carbamate (urethane), as well as X-ray irradiation. With the chemical carcinogenesis models, no mutations were detected in Egfr, which is in clear contrast to the high rates observed in either codon 12 or 61 of K-ras (21/23 of the lung tumors induced with NNK, 4/5 with MeIQx, 1/4 with urethane and 7/18 with BHP). However, in the X-ray-induced lung tumors, Egfr mutations with amino acid substitution were observed in exons 18 and 21 (4/12, 33%), but no activating mutation of K-ras was detected. In addition, one and four silent mutations were identified in K-ras (exon 1) and Egfr (exons 18, 20 and 21), respectively. Most mutations in both Egfr and K-ras were G/C-->A/T transitions (7/8, 88% and 31/34, 91%, respectively). Although, the mutational patterns in equivalent human lesions were not completely coincident, this first report of Egfr mutations in an experimental lung tumor model suggests that X-rays or other factors producing oxygen radicals could cause EGFR mutations in some proportion of lung cancers in humans.
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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/4-(N-methyl-N-nitrosamino)-1-(3-pyri...,
http://linkedlifedata.com/resource/pubmed/chemical/Carcinogens,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrosamines,
http://linkedlifedata.com/resource/pubmed/chemical/Urethane,
http://linkedlifedata.com/resource/pubmed/chemical/diisopropanolnitrosamine
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1349-7006
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pubmed:author |
pubmed-author:ImaidaKatsumiK,
pubmed-author:KitahashiTsukasaT,
pubmed-author:OghisoYoichiY,
pubmed-author:SugimuraTakashiT,
pubmed-author:TakahashiMamiM,
pubmed-author:TakasukaNobuoN,
pubmed-author:TsutsumiMasahiroM,
pubmed-author:WakabayashiKeijiK,
pubmed-author:YamadaYutakaY,
pubmed-author:YokohiraMasanaoM
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pubmed:issnType |
Electronic
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pubmed:volume |
99
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
241-5
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pubmed:meshHeading |
pubmed-meshheading:18271921-Animals,
pubmed-meshheading:18271921-Base Sequence,
pubmed-meshheading:18271921-Carcinogens,
pubmed-meshheading:18271921-Exons,
pubmed-meshheading:18271921-Female,
pubmed-meshheading:18271921-Genes, erbB-1,
pubmed-meshheading:18271921-Genes, ras,
pubmed-meshheading:18271921-Lung Neoplasms,
pubmed-meshheading:18271921-Mice,
pubmed-meshheading:18271921-Mice, Inbred Strains,
pubmed-meshheading:18271921-Molecular Sequence Data,
pubmed-meshheading:18271921-Mutation,
pubmed-meshheading:18271921-Neoplasms, Radiation-Induced,
pubmed-meshheading:18271921-Nitrosamines,
pubmed-meshheading:18271921-Rats,
pubmed-meshheading:18271921-Urethane,
pubmed-meshheading:18271921-X-Rays
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pubmed:year |
2008
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pubmed:articleTitle |
Occurrence of mutations in the epidermal growth factor receptor gene in X-ray-induced rat lung tumors.
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pubmed:affiliation |
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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