乙型肝炎病毒相关性肝癌与p53基因变化的关系

Relationship between hepatitis B virus associated primary hepatocellular carcinoma and alteration of tumor suppressor gene p 53

目的：探讨与ＨＢＶ感染相关的肝癌其ｐ５３基因变化及意义．方法：收集１６例西安地区的肝癌及其癌旁肝组织，应用Ｓｏｕｔｈｅｒｎ杂交检测了组织中ＨＢＶＤＮＡ的状态．免疫组化确定ＨＢＶ的ＨＢｓＡｇ，ＨＢｘＡｇ和肿瘤抑制基因Ｐ５３蛋白的分布，采用ＰＣＲ扩增后直接ＤＮＡ序列分析，检测了ｐ５３基因第５～８外显子的基因序列．结果：１６例中１３例ＨＢＶＤＮＡＳｏｕｔｈｅｒｎ杂交阳性，１０例癌组织和１３例癌旁组织ＨＢｘＡｇ染色阳性，９例Ｐ５３蛋白染色阳性．ｐ５３基因序列分析５例存在点突变，其中仅１例位于２４９编码区．结论：与ＨＢＶ感染密切相关的肝癌，ｐ５３基因第２４９编码区的点突变并不显著，进一步表明细胞内Ｐ５３蛋白积聚可能与ＨＢｘＡｇ的存在有关，二者以结合的形式存在并使ｐ５３功能失活在肝癌的发生机制中具有重要意义．

Aim: To explore the changes and significance of tumor suppressor gene p 53 in primary hepatocellular carcinoma (PHC) with hepatitis B virus (HBV) infection. Methods: Sixteen cases of PHC were studied by Southern hybridization to detect the state of HBV DNA in tissues, by immunohistochemical staining to determine HBsAg, HBxAg and P53 protein, and by PCR directed sequencing to analyse the point mutation of p 53 gene exon 5 to 8. Results: Thirteen of sixteen cases showed the HBV DNA positive, 10 cases tumor and 13 cases nontumor tissues showed the HBxAg positive, and 9 cases were positive for P53 protein. The sequencing of p 53 gene revealed the point mutation in 5 cases. Among them only 1 case was sited at codon 249 G to T. Conclusion: The mutation of p 53 gene codon 249 is in frequence in HBV related PHC, the accumulation of P53 protein in cells may be associated with expression of HBxAg. HBxAg binding to P53 protein and inactivation of p 53 function play important roles in the development of PHC.