Activation of c-myc by woodchuck hepatitis virus insertion in hepatocellular carcinoma

doi:10.1016/0092-8674(88)90221-8

Cell

Volume 55, Issue 4, 18 November 1988, Pages 627-635

https://doi.org/10.1016/0092-8674(88)90221-8 Get rights and content

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.

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What these are remains unknown. In a small fraction of woodchuck HCCs, proximal integration of WHV DNA along with transcriptional activation may be found instead at N-myc1 or C-myc (Fourel et al., 1990; Hsu et al., 1988). To address issues related to the oncogenicity of C-myc and N-myc2, Buendia and colleagues made transgenic mice containing either WHV/Nmyc2 or WHV/Cmyc DNA fragments cloned from woodchuck HCCs (Renard et al., 2000; Terradillos et al., 1997).
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ArticleActivation of c-myc by woodchuck hepatitis virus insertion in hepatocellular carcinoma

Abstract

Cell

Plasmid

Cell

Cell

Cell

Cell

Epidemiology of hepatocellular carcinoma

Novel promoter upstream of the human c-myc gene and regulation of c-myc expression in B-cell lymphomas

Mol. Cell. Biol.

C-myc deregulation by chromosomal translocation in Burkitt's lymphoma

Identification of a second human retinoic acid receptor

Nature

Hepatitis B virus DNA integration in a sequence homologous to v-erb-A and steroid receptor genes in a hepatocellular carcinoma

Nature

The tandem direct repeats within the long terminal repeat of murine leukemia viruses are the primary determinant of their leukemogenic potential

J. Virol.

A novel steroid thyroid hormone receptor-related gene inappropriately expressed in human hepatocellular carcinoma

Nature

Neoplasms of the liver

The molecular biology of hepatitis B viruses

Annu. Rev. Biochem.

Regulatory elements that modulate expression of human c-myc

Genes Dev.

Characterization of rat c-myc and adjacent regions

Nucl. Acids Res.

Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis

Nature

Hepatitis B virus integration site in hepatocellular carcinoma at chromosome 17, 18 translocation

The human hepatitis B virus enhancer requires trans-acting cellular factor(s) for activity

Mol. Cell. Biol.

Nucleotide sequence of a cloned woodchuck hepatitis virus genome: evolutional relationship between hepadnaviruses

J. Virol.

Recombination between two integrated proviruses, one of which was inserted near c-myc in a retrovirus-induced rat thymoma: implications for tumor progression

J. Virol.

Viral integration near c-myc in 10–20% of MCF 247-induced AKR lymphomas

Proteolytic self-cleavage of hepatitis B virus core protein may generate serum e antigen

Science

Transcription of woodchuck hepatitis virus in the chronically infected liver

EMBO. J.

Rearrangement and enhanced expression of c-myc in hepatocellular carcinoma of hepatitis virus infected woodchucks

Nature

Article
Activation of c-myc by woodchuck hepatitis virus insertion in hepatocellular carcinoma