人宫颈癌发生中p16INK4A表达缺陷与其外显子甲基化的关系  

Disfigurement of p16INK4A gene expression in development of cervical cancer and study of the mechanism

作　　者：李敏[1] 吴素慧[2] 贺小红[1] 王瀚[1] 李晓艳[1] 董卫红[1] 王泽华[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院妇产科,武汉430022 [2]山西医科大学第一临床医学院妇产科

出　　处：《山西医科大学学报》2006年第1期42-45,共4页Journal of Shanxi Medical University

基　　金：国家自然科学基金资助项目(NO.30070786)

摘　　要：目的研究抑癌基因p16I NK4A在宫颈癌发生中的表达变化,分析这种差异表达与甲基化的关系。方法逆转录聚合酶链技术(RT-PCR)检测30例宫颈癌组织标本、48例宫颈上皮内瘤样病变(CI N)组织(CI NⅠ12例、CI NⅡ16例、CI NⅢ20例)中p16I NK4A基因的表达。Western Blot分析P16I NK4A蛋白水平的表达。甲基化特异性的PCR技术(MSP)对p16I NK4A DNA进行甲基化分析。以每例标本相应正常宫颈组织作为对照。结果70%(21/30)宫颈癌组织中p16I NK4A表达下降或缺失,与正常宫颈组织、CI NⅠ和CI NⅡ中的p16I NK4A表达相比,差异具有统计学意义(P<0.05),与CI NⅢ相比差异无统计学意义(P>0.05)。蛋白的表达检测也得到相似的结果。MSP检测发现宫颈癌组织中有9例p16I NK4A外显子甲基化,甲基化率为30%,其中8例年龄小于40岁,提示甲基化易于出现在年轻患者。而CI N组织中仅CI NⅢ发现1例甲基化,说明甲基化随着宫颈病变的发展而增多。分析甲基化与p16I NK4A表达的关系,发现42.86%(9/21)的宫颈癌组织中p16I NK4A表达下降与甲基化有关,甲基化的宫颈癌组织中p16I NK4A表达均下降。结论p16I NK4A作为一种抑癌基因,它的表达缺失或下降在宫颈癌的发生中起重要作用,外显子甲基化是导致其表达缺陷的部分原因。Objective To evaluate the expression of p16INK4A gene in cervical cancer and analyze the relation between this alteration and the promoter methylation of p16INK4A DNA. Methods Thirty cervical cancer tissues and thirty-eight cervical intraepithelial neoplasia （CIN） tissues were chosen. The level of p16INK4A mRNA was detected with reverse transcription polymerase chain reaction （RT-PCR）. Protein was tested by Western Blot. Methylation specific PCR （MSP） was used to check whether it was methylated in the tin,motet of p16INK4A exon. Normal cervical tissues were used as control. Results Compared with the contrd, the expression of p16INK4A mRNA in cervical cancer decreased significantly or absolutely defaulted, and expression of p16INK4A protein also decreased（P〈0.05）. Nine cervical cancer specimens were found methylated in the exon of p16INK4A and the rate was 30%. 42.86% decreasing expression was related to p16INK4A methylation, all the methylated tissues were expressed lower p16INK4A. What＇s more, methylation was related with the age and stage of the patients, it was predisposed to occur in younger and late stage patients. Conclusion That disfigurement of p16INK4A gene expression plays an important role in the development of cervical cancer, and this alteration is partially caused by methylation of p16INK4A exon.

关 键 词：P16INK4A 宫颈癌 甲基化 

分 类 号：R737.33[医药卫生—肿瘤]