Hepatitis B virus and hepatocellular carcinoma: a possible role for the viral transactivators.
Several epidemiological studies have demonstrated a link between chronic B virus infection and primary hepatocellular carcinoma (PHC). HBV DNA sequence integrations into the host cell genome have often been observed in hepatocarcinoma tissues. However, since only in a few cases of PHC the target of HBV-DNA insertion has been identified, alternative mechanisms for HBV-induced hepatocyte transformation have been investigated. Like many other DNA viruses, the hepatitis B virus bears a transactivational potential. Both full length and truncated versions of HBV X protein are able to influence the expression of cellular nuclear protooncogenes c-fos and c-myc. A second transcriptional activator is encoded by the PreS/S region of HBV, but its activity on viral and cellular genes become evident only after dislocations from its downstream sequences. Thus, HBV is able to influence infected cell growth and differentiation using both native proteins, newly generated truncated proteins and virus-cell fusion polypeptides.
Levrero
M
M
I Clinica Medica e Fondazione Andrea Cesalpino, Policlinico Umberto I, Roma, Italy.
Balsano
C
C
Avantaggiati
M L
ML
Natoli
G
G
De Marzio
E
E
Will
H
H
D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000382:microbiology*; D016762:Genes, fos; D016259:Genes, myc; D006509:Hepatitis B / Q000150:complications*; D006511:Hepatitis B Antigens / Q000502:physiology*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000382:microbiology*; D015534:Trans-Activators / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins
D006511:Hepatitis B Antigens; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein