Modification of cyclin A expression by hepatitis B virus DNA integration in a hepatocellular carcinoma

• Published in: Oncogene Vol. 7; no. 8; p. 1653
• Main Authors: Wang, J, Zindy, F, Chenivesse, X, Lamas, E, Henglein, B, Bréchot, C
• Format: Journal Article
• Language: English
• Published: England 01-08-1992
• Subjects: Base Sequence; Blotting, Northern; Carcinoma, Hepatocellular - genetics; Cell Transformation, Neoplastic - genetics; Cyclins - genetics; DNA, Viral - genetics; Hepatitis B virus - genetics; Humans; Introns - genetics; Liver Neoplasms - genetics; Molecular Sequence Data; Mutagenesis, Insertional - genetics; Proviruses - genetics; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Virus Integration
• ISSN: 0950-9232

We have previously reported the identification of a hepatitis B virus (HBV) DNA integration in an intron of the cyclin A gene in an early hepatocellular carcinoma (HCC) and the isolation of human cyclin A cDNA. We have now constructed a cDNA library from the tumor and isolated several hybrid HBV-cyclin A cDNAs from it. The hybrid cDNAs encode an HBV-cyclin A fusion protein. In the chimeric protein, the N-terminus of cyclin A, including the signals for cyclin degradation, is deleted and replaced by viral PreS2/S sequences, transcription being initiated from the viral PreS2/S promoter. This chimeric protein is undegradable in an in vitro cyclin degradation assay. Northern blot analyses showed strong expression of the hybrid transcripts in the tumor, while cyclin A- or HBV-specific transcripts were not detected in the non-tumorous liver of the same patient. Thus, HBV DNA integration in the cyclin A gene resulted in a strong expression of hybrid HBV-cyclin A transcripts encoding a stabilized cyclin A. This chimeric protein may play an important role in the development of the tumor.