Modification of cyclin A expression by hepatitis B virus DNA integration in a hepatocellular carcinoma.
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.
Wang
J
J
INSERM U75, CHU Necker, Paris, France.
Zindy
F
F
Chenivesse
X
X
Lamas
E
E
Henglein
B
B
Bréchot
C
C
D001483:Base Sequence; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D016213:Cyclins / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000235:genetics; D011533:Proviruses / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016662:Virus Integration
D016213:Cyclins; D004279:DNA, Viral; D011993:Recombinant Fusion Proteins