53基因密码子249突变致肝细胞癌的机理研究

Study on the mechanism through which Codon 249 mutations of p53 gene induce the formation hepatocellular carcinoma

目的为了进一步探讨ＨＣＣ中ｐ５３基因密码子２４９突变的作用机理。方法收集密码子２４９突变率为３２９％的７０例南方地区手术切除ＨＣＣ标本，采用ＳＳＣＰ、ＩＨＣ和ＲＮＡ斑点杂交分析方法，深入研究了密码子２４９突变伴ＬＯＨ情况及其对ｐ５３基因转录和翻译的影响。结果９０％的密码子２４９突变伴ＬＯＨ。突变组中，ｐ５３蛋白和ｐ５３ｍＲＮＡ检出率分别为９１３％和９５７％，两者均显著高于无突变组（Ｐ＜０００１）。相关分析显示，ｐ５３基因的转录与翻译之间高度相关（ｒ＝０．８２０８）。结论ＬＯＨ是使ｐ５３基因密码子２４９突变发挥致癌作用的主要因素。ｐ５３基因密码子２４９的突变导致了ｐ５３基因在转录和翻译两水平上的增加。

im In order to investigate the mechanism through which Codon 249 induce the formation of hepatocellular carcinoma. Methods LOH accompaniment of Codon 249 mutation and its effect to tramslation and transcription using SSCP,IHC and RTPCR/slot hybriddization were studiedd.Results Codon 249mutation was accompanied by LOH in 90%.The positive rates of p53 protein and mRNA were 91.3% and 95.7% respectively in mutation group.Both of them were significantly higher than those in nonmutation group(p〈0.001).The translation of p53 gene was strongly related to its transcription by correlate analysis(r=0.8208).Conclusions LOH might pay important role in hepatocarcinogenesis if Codon 249 mutation.Codon 249 mutation could increase both transcription and tramslation of p53 gene.The increased expression of p53 protein mainly depended on the increased transcreption of p53 gene.