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Frequent mutations of the Trp53, Hras1 and β-catenin (Catnb) genes in 1,3-butadiene-induced mammary adenocarcinomas in B6C3F1 mice

DNAs from 1,3-butadiene-induced mammary adenocarcinomas of B6C3F1 mice were examined for mutations in the Trp53 gene, the ras gene family and several components of the Wnt signaling pathway, including beta -catenin (Catnb), Apc and Axin. Trp53 mutations were detected in 41% (7 out of 17) of tumors.... Full description

Journal Title: Oncogene 2002, Vol.21(36), p.5643
Main Author: Shi-Mei Zhuang
Other Authors: Roger W Wiseman , Peter Söderkvist
Format: Electronic Article Electronic Article
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ID: ISSN: 0950-9232 ; E-ISSN: 1476-5594 ; DOI: 10.1038/sj.onc.1205649
Link: http://dx.doi.org/10.1038/sj.onc.1205649
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recordid: nature_a10.1038/sj.onc.1205649
title: Frequent mutations of the Trp53, Hras1 and β-catenin (Catnb) genes in 1,3-butadiene-induced mammary adenocarcinomas in B6C3F1 mice
format: Article
creator:
  • Shi-Mei Zhuang
  • Roger W Wiseman
  • Peter Söderkvist
subjects:
  • Rodentia (Mice)
  • Ras and Ras Related Oncogenes (Rho/Rac/Ral)
  • Apc Gene
  • Axin Gene
  • Hras1 Gene
  • Trp53 Gene
  • Beta -Catenin
  • Chemical Carcinogenesis
  • Mice
ispartof: Oncogene, 2002, Vol.21(36), p.5643
description: DNAs from 1,3-butadiene-induced mammary adenocarcinomas of B6C3F1 mice were examined for mutations in the Trp53 gene, the ras gene family and several components of the Wnt signaling pathway, including beta -catenin (Catnb), Apc and Axin. Trp53 mutations were detected in 41% (7 out of 17) of tumors. Each tumor with a Trp53 mutation also exhibited loss of the wild-type Trp53 allele, supporting the importance of Trp53 inactivation during development of these tumors. Analyses of the Hras1, Kras2 and Nras proto-oncogenes revealed Hras1 mutations in 53% (9 out of 17) of tumors. Seven of these mutations were a G arrow right C transversion in Hras1 codon 13, consistent with a 1,3-butadiene-specific Kras2 mutation previously reported in several other tumor types. Mutation screens in Catnb exon 2, the Apc mutation cluster region and the Catnb-binding domain of the Axin gene identified Catnb missense mutations in 3 out of 17 (18%) tumors. In total, mutations of the Trp53, Hras1 and/or Catnb genes were identified in 15 out of 17 1,3-butadiene-induced mammary adenocarcinomas. These results indicate that multiple genetic pathways are disrupted in chemically induced mammary tumors, and that studies in mouse models may help to understand the etiology of human breast cancers.
language:
source:
identifier: ISSN: 0950-9232 ; E-ISSN: 1476-5594 ; DOI: 10.1038/sj.onc.1205649
fulltext: fulltext
issn:
  • 0950-9232
  • 09509232
  • 1476-5594
  • 14765594
url: Link


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titleFrequent mutations of the Trp53, Hras1 and β-catenin (Catnb) genes in 1,3-butadiene-induced mammary adenocarcinomas in B6C3F1 mice
creatorShi-Mei Zhuang ; Roger W Wiseman ; Peter Söderkvist
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subjectRodentia (Mice) ; Ras and Ras Related Oncogenes (Rho/Rac/Ral) ; Apc Gene ; Axin Gene ; Hras1 Gene ; Trp53 Gene ; Beta -Catenin ; Chemical Carcinogenesis ; Mice;
descriptionDNAs from 1,3-butadiene-induced mammary adenocarcinomas of B6C3F1 mice were examined for mutations in the Trp53 gene, the ras gene family and several components of the Wnt signaling pathway, including beta -catenin (Catnb), Apc and Axin. Trp53 mutations were detected in 41% (7 out of 17) of tumors. Each tumor with a Trp53 mutation also exhibited loss of the wild-type Trp53 allele, supporting the importance of Trp53 inactivation during development of these tumors. Analyses of the Hras1, Kras2 and Nras proto-oncogenes revealed Hras1 mutations in 53% (9 out of 17) of tumors. Seven of these mutations were a G arrow right C transversion in Hras1 codon 13, consistent with a 1,3-butadiene-specific Kras2 mutation previously reported in several other tumor types. Mutation screens in Catnb exon 2, the Apc mutation cluster region and the Catnb-binding domain of the Axin gene identified Catnb missense mutations in 3 out of 17 (18%) tumors. In total, mutations of the Trp53, Hras1 and/or Catnb genes were identified in 15 out of 17 1,3-butadiene-induced mammary adenocarcinomas. These results indicate that multiple genetic pathways are disrupted in chemically induced mammary tumors, and that studies in mouse models may help to understand the etiology of human breast cancers.
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