title: Activation of c-myc by woodchuck hepatitis virus insertion in hepatocellular carcinoma.
abstract: Two hepatocellular carcinomas, induced in woodchucks chronically infected with woodchuck hepatitis virus, were characterized for viral integration near c-myc and alterations of c-myc expression. In one tumor, viral integration within the untranslated region of c-myc exon 3 resulted in overexpression of a long c-myc viral cotranscript. In the second tumor, a single insertion of highly rearranged viral sequences 600 bp upstream of c-myc exon 1 was associated with increased levels of normal c-myc mRNA. In both cases, viral enhancer insertion and disruption of normal c-myc transcriptional or posttranscriptional control appear to be involved in c-myc activation. These results demonstrate that integration of woodchuck hepatitis virus near a cellular proto-oncogene, as in several retroviral models, can contribute to the genesis of liver tumors.
authors.affiliation: Unité de Recombinaison et Expression Génétique Institut Pasteur, Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Hsu
authors.forename: T
authors.initials: T
authors.lastname: Möröy
authors.forename: J
authors.initials: J
authors.lastname: Etiemble
authors.forename: A
authors.initials: A
authors.lastname: Louise
authors.forename: C
authors.initials: C
authors.lastname: Trépo
authors.forename: P
authors.initials: P
authors.lastname: Tiollais
authors.forename: M A
authors.initials: MA
authors.lastname: Buendia
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D006524:Hepatitis, Viral, Animal / Q000235:genetics* / Q000382:microbiology; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000382:microbiology*; D008392:Marmota; D008969:Molecular Sequence Data; D009857:Oncogenes; D011519:Proto-Oncogenes; D014158:Transcription, Genetic