MDM2蛋白过度表达致p53功能失活在原发性肝细胞癌发生中的作用  

Role of functional inactivation of p53 from MDM2 overexpression in hepatocarcinogenesis

作　　者：罗育林[1] 程瑞雪[1] 冯德云[1] 付春燕[1] 沈明[1] 

机构地区：[1]中南大学湘雅医学院病理学教研室,长沙410078

出　　处：《湖南医科大学学报》2001年第1期13-16,共4页Bulletin of Hunan Medical University

摘　　要：目的 :研究p5 3基因突变及p5 3,MDM2蛋白表达在原发性肝细胞癌 (HCC)发生中的作用。方法 :应用免疫组织化学SP法检测 6 1例原发性肝细胞癌及 5 9例相应癌旁肝组织中p5 3蛋白和MDM2蛋白的表达 ;用PCR -SSCP-银染技术对其中 2 1例HCC的p5 3基因第 5～ 8外显子的突变情况进行研究。结果 :p5 3和MDM2蛋白在HCC中的表达明显高于癌旁肝组织 (P <0 .0 1)。HCC中p5 3与MDM2蛋白表达无明显相关性 (P >0 .0 5 )。新鲜HCC组织中p5 3基因第 5～ 8外显子的突变率为 42 .86 % (9/ 2 1) ,且均位于第 7外显子 ,癌旁组织中未发现p5 3基因突变。突变病例中 6 6 .6 7% (6 / 9)有p5 3蛋白高表达 ,11.11% (1/ 9)有p5 3及MDM2蛋白的过度表达 ,无突变病例中MDM2过度表达率为 2 5 % (3/ 12 )。结论 :p5 3基因突变及由MDM2过度表达导致的p5 3功能失活在HCC发生中起重要作用。p5 3基因突变和其它机制引起的MDM2蛋白高表达可能在HCC中共同发挥致癌作用。Objective: This paper was to evaluate the role of p53 mutation,and p53 and MDM2 proteins expression in hepatocarcinogenesis. Methods: Using streptavidin-peroxidase conjugation method (SP), the expression of p53 and MDM2 proteins was observed in 61 cases of primary hepatocarcinomas (HCC) and 59 cases of corresponding paracancerous tissue, among which p53 mutations in exons 5～8 were detected in 21 cases by polymerase chain reaction single-strand confirmation polymorphism analysis (PCR-SSCP). Results:Positive nuclear p53 and MDM2 immunostainings were demonstrated in 57.38% (35/61) and 26.23% (16/61) of HCC, and 1.69% (1/59) and 3.39% (2/59) of corresponding paracancerous tissue, respectively. The expressions of p53 and MDM2 proteins in HCCs were significantly higher than those in paracancerous tissues (P<0.01). The expressions of p53 and MDM2 were not significantly correlated (P>0.05). There were 42.86% (9/21) mutations in exon 7 of p53 gene and no mutation was observed in exons 5, 6, 8 in HCCs and in paracancerous tissues. In cases of p53 mutations, there were 66.67% (6/9) of p53 overexpression and 11.11% (1/9) of overexpression of both p53 and MDM2. MDM2 overexpression also appeared in 25% (3/12) of cases without mutation. Conclusions: Mutation of p53 gene and functional inactivation of p53 resulting from MDM2 overexpression play an important role in carcinogenesis of HCC. It is possible that p53 mutations and MDM2 overexpression induced by other mechanisms are involved in carcinogenesis of HCC. [

关 键 词：P53蛋白 原发性肝细胞癌 MDM2 基因突变 PCR-SSCP 免疫组织化学 蛋白过度表达 

分 类 号：R735.7[医药卫生—肿瘤] R730.231[医药卫生—临床医学]