[Hepatitis B X Antigen Binding to P53 Protein in the Pathogenesis of Primary Hepatocellular Carcinoma]

Much evidences have showed a close relation between HBV infection and the development of primary hepatocellular carcinoma (PHC). Molecular genetic study showed loss of heterozygosity in PHC and that point mutation of p53 exon 7 at codon 249 was important to PHC. But these changes of PHC associated with aflatoxin B1 and HBV were not apparent. Thirteen cases of PHC were examined to determine whether there were any relationship between HBxAg and p53 protein. HBV-DNA was integrated to PHC tissue in 9 of the 13 cases by southern blot; HBsAg, HBxAg or HBcAg was found in 8 by immunohistochemical staining. None had the point mutation of p53 exon 7 at codon 229, 247 and 249 by PCR and restriction enzymes. Immunoprecipitation analyses were carried out to test whether anti-X antibody was capable of precipitating p53 or anti-p53 could immunoprecipitate HBxAg polypeptides from HBV infected tissue. Specific band was detected at 53,000 in 7 of the 13 cases as precipitating with anti-HBxAg and western blotting using anti-p53, and specific band was detected at 13,000, 17,000 or 28,000 in 6 of the 13 cases as precipitating with anti-p53 and western blotting using anti-HBxAg. These results revealed that the binding of HBxAg to p53 may be analogous to that observed in tumor antigen encoded from selected papovaviruses, and adenoviruses, and may be a crucial step in the development of PHC among most HBV infected patients.