Hepatitis B virus (
HBV) X protein is thought to play an important role in the development of
hepatocellular carcinoma. Recent studies on a transgenic mouse
tumor model suggest that
HBV X protein may contribute to transformation by binding to and inactivating the cellular growth suppressor
protein p53. We have studied 31
hepatocellular carcinoma tissues from Chinese patients for the possible occurrence of such interactions. Although most of the samples contained markers of HBV
infection, including free and/or integrated HBV
DNA, there was no detectable expression of
HBV X protein by Western blot, immunoprecipitation, or histochemical staining. There was also no evidence of
HBV X protein associated with p53 immunoprecipitated from the
tumors. These observations suggest that, in naturally occurring human
hepatocellular carcinoma, such interactions are uncommon and, therefore, unlikely to be of relevance in the latter stages of
tumor development. On the other hand, 29 of 31 (93%) samples contained mutated forms of p53, as determined by various
antibodies that detect wild-type or mutant p53 or both, and by the association of
heat shock protein 70 with immunoprecipitated p53. These results show that conformationally altered p53
protein is present in
tumors at a much higher frequency than is suggested by the presence of known mutations in the gene. This mutant p53 is functionally inactive, as suggested by the lack of expression of the p53-induced M(r) 21,000 Cip1/Waf1
protein in the
tumors. Because this inactivation of p53 was not correlated with the expression of
HBV X protein, any interaction of
HBV X protein with p53 may be relevant only during acute
infection. Such an interaction could serve to relax cell growth control at a time when virus replication requires hepatocyte destruction to be balanced by regeneration.