Wip1基因在人脑胶质瘤组织中的表达及其与p53基因突变的相关性研究  

Selectively overexpression of Wip1 gene and the correlation with p53 mutation in human astrocytomas

作　　者：王鹏[1] 饶竞[1] 杨海峰[1] 姚东晓[1] 赵洪洋[1] 杨林[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院神经外科,湖北武汉430022

出　　处：《中国癌症杂志》2010年第7期481-485,共5页China Oncology

基　　金：国家自然科学基金项目(项目编号:30772240)

摘　　要：背景与目的:野生型p53诱导的磷酸酶1(wild-type p53-induced phosphatase1,Wip1)是一种新发现的癌基因,其在多种肿瘤中存在过表达。本研究旨在探讨Wip1基因在脑胶质瘤组织中的表达及其与p53基因突变的相关性。方法:收集52例原发胶质瘤及8例脑外伤或脑出血后行内减压术的正常脑组织标本,采用实时荧光定量PCR(real-time fluorogentic quantitative,RFQ-PCR)法检测脑胶质瘤组织中Wip1mRNA的表达,Western blot法检测Wip1蛋白的表达,DNA直接测序法检测脑胶质瘤组织中p53基因的突变情况。统计学分析不同脑胶质瘤病理分级及p53的突变状态间Wip1的表达水平的差异。结果:52例脑胶质瘤中22例(42.3%)发生p53基因突变。Wip1 mRNA在高级别胶质瘤(Ⅲ～Ⅳ级)中的表达水平较低级别胶质瘤(Ⅰ～Ⅱ级)及正常脑组织中的表达要略高,但差异无统计学意义(P<0.05)。Wip1基因在无p53基因突变的胶质瘤组织中的表达水平较p53基因突变组要高,差异有统计学意义(P=0.009)。Wip1在野生型p53的胶质瘤中存在选择性的过表达,Wip1在胶质瘤中的过表达与病理分级无明显相关,而与p53的突变状态有关。结论:Wip1基因在脑胶质瘤中存在选择性地过表达,其过表达与p53基因野生型状态相关,可能是胶质瘤恶性进展中除p53基因突变外的另一关键作用因素。Background and purpose：Malignant astrocytomas are the most common brain tumors.The activation,over-expression or amplification of some oncogenes as well as the deletion or inactivation of tumor suppressor genes may be involved in the formation of glioma and malignant transformation.p53 plays a key role in preventing cancer progression as it is often mutated in many tumors,including brain tumors.Wild-type p53-induced phosphatase 1 （Wip1） is overexpressed in many cancers.This study investigated the expression of the Wip1 gene in human astrocytomas and its relationship with p53 mutation.Methods：Fifty-two cases of human astrocytomas and 8 cases of normal brain tissues were collected in our hospital.All samples were evaluated for the mutation at exon 5-8 of p53 gene with the use of DNA sequencing of genomic DNA.The Wip1 mRNA expression was examined through real-time quantitative polymerase chain reaction.Protein expression of Wip1 of human astrocytomas was determined through western blot analysis.The statistical analysis was conducted in order to show significant differences between the expression level of Wip1 based on pathological grade and the mutational status of the p53 gene.Results：p53 gene mutations were found in 22 of the 52 astrocytoma samples （42.3%）.The mRNA expression of Wip1 in high-grade pathology （WHO Ⅲ-Ⅳ） showed slightly elevated when compared with that in low-grade astrocytomas （WHO Ⅰ-Ⅱ） and normal brain tissues,but the difference did not reach statistical significance （P=0.305）.However,the expression of Wip1 tumor samples with wild-type p53 showed significantly elevated mRNA expression in comparison to the samples with mutant p53 （P=0.009）.The Wip1 gene was also found to be selectively overexpressed in human astrocytomas with wild-type p53.This means that the overexpression of Wip1 in astrocytomas was not exactly relevant to the pathological grade,but associated with the status of p53.The protein expression of Wip1 detected by western blot showed that it is in co

关 键 词：胶质瘤 Wip1基因 P53 基因突变 

分 类 号：R730.264[医药卫生—肿瘤]