p53异构体与胃癌发生发展的相关性及其机制  

Relevance of p53 isoforms in genesis and progression of gastric cancer

作　　者：张红梅[1] 张小茜[1] 仲华[1] 张娜[2] 李蕾[1] 季万胜[1] 

机构地区：[1]潍坊医学院附属医院消化内科,山东省潍坊市261031 [2]潍坊医学院,山东省潍坊市261053

出　　处：《世界华人消化杂志》2013年第28期2922-2928,共7页World Chinese Journal of Digestology

基　　金：山东省优秀中青年科学家科研奖励基金资助项目;No.BS2010SW034

摘　　要：目的:探讨p53异构体与胃癌发生、发展中的相关性及其机制.方法:收集胃癌、萎缩性胃炎、正常胃黏膜组织各30例,应用NT-PCR法及免疫组织化学方法检测3组中的p53异构体p53、133p53和PTEN、Bax、p21waf1/cip1基因的表达情况,并进行统计学分析.结果:p53在胃癌、慢性萎缩性胃炎及正常胃黏膜组织中的表达率分别为26.7%、33.3%和70.0%,胃癌组织p53的表达明显低于正常胃组织(P<0.01);133p53在胃癌、慢性萎缩性胃炎及正常胃黏膜组织中的表达率分别为70.0%、50.0%,23.3%,胃癌组织133p53的表达明显高于正常胃组织(P<0.01);PTEN在胃癌、慢性萎缩性胃炎及正常胃黏膜组织中的表达率分别为53.3%、76.7%、86.7%;Bax在胃癌、慢性萎缩性胃炎及正常胃黏膜组织中的表达率分别为36.7%、73.3%、83.3%;p21waf1/cip1在胃癌、慢性萎缩性胃炎及正常胃黏膜组织中的表达率分别为46.7%、50.0%、86.7%,胃癌组织中P T E N、B a x及p21waf1/cip1的表达均明显低于正常胃组织(P<0.05).p53和PTEN、Bax、p21waf1/cip1在胃癌中表达均呈正相关关系,而133p53和PTEN、Bax、p21waf1/cip1在胃癌中表达均呈负相关关系(P<0.05).结论:p53异构体p53、133p53在胃癌中的差异性表达,可能通过调控Bax、p21waf1/cip1及PTEN等下游基因而抑制p53的活性,对胃癌的发生发展产生了重要作用.AIM： To investigate the relevance of p53 isoforms in the genesis and development of gastric cancer and to explore possible mechanisms involved.METHODS： Ninety specimens of gastric cancer,atrophic gastritis and normal gastric mucosa were gathered.The expression of p53 splice variants（p53β,Δ133p53）,PTEN,Bax,and p21waf1/cip1 in the above specimens was detected by nested reverse transcription-polymerase chain reaction（NT-PCR）and immunohistochemistry.RESULTS： The positive rate of p53 expression was significantly lower in gastric cancer and atrophic gastritis than in normal gastric mucosa（26.7%,33.3% vs 70.0%,both P 0.01）.The positive rate of Δ133p53 expression was 70.0% in gastric cancer,50.0% in atrophic gastritis,and23.3% in normal gastric mucosa,which was significantly higher in gastric cancer than in normal gastric mucosa（P 0.01）.The positive rate of PTEN expression was 53.3% in gastric cancer,76.7% in atrophic gastritis,and 86.7% in normal gastric mucosa,and the corresponding percentages were 36.7%,73.3% and 83.3% for Bax,and46.7%,50.0% and 86.7% for p21waf1/cip1.The positive rates of PTEN,Bax and p21waf1/cip1expression were significantly lower in gastric cancer than in normal gastric mucosa（all P 0.05）.There were positive correlations between the expression of p53 and PTEN,p53 and Bax,p53 and p21waf1/cip1,and negative correlations between the expression of Δ133p53 and PTEN,Δ133p53 and Bax,Δ133p53 and p21waf1/cip1 in gastric cancer（all P 0.05）.CONCLUSION： Differential expression of p53 and Δ133p53 in gastric cancer may suppress the activity of p53 by regulating Bax,p21waf1/cip1and PTEN and thereby affect the genesis and development of gastric cancer.

关 键 词：P53异构体 P53β △133p53 同源丢失性磷酸酶张力蛋白 BAX基因 P21WAF1 cip1基因 胃癌 

分 类 号：R735.2[医药卫生—肿瘤]