抑癌基因PTEN在鼻咽癌中的突变及表达  

Mutation and expression of tumor suppressor gene PTEN in patients with nasopharyngeal carcinoma

作　　者：杨时平[1] 马骏[1] 应小芳[2] 孟祥祺[2] 黄文林[2] 

机构地区：[1]中山大学肿瘤防治中心放疗科,广州510060 [2]华南肿瘤学国家重点实验室

出　　处：《解放军医学杂志》2009年第7期868-870,880,共4页Medical Journal of Chinese People's Liberation Army

基　　金：国家重点基础研究发展计划(973计划)资助项目(2004CB51880)

摘　　要：目的探讨抑癌基因PTEN在鼻咽癌细胞株及组织中的基因突变和蛋白表达缺失情况。方法收集鼻咽癌细胞株4种(CNE-1、CNE-2、HONE1、SUNE1)、经病理组织学确诊为未分化型非角化性鼻咽癌组织标本96例(其中71例同时取癌旁组织)和慢性鼻咽炎的组织标本5例。4种鼻咽癌细胞株、25例未分化型非角化性鼻咽癌组织和5例慢性鼻咽炎组织标本用于检测基因突变,其余71例未分化型非角化性鼻咽癌组织及癌旁组织进行免疫组化,检测PTEN的蛋白表达。采用RT-PCR和直接测序法分析PTEN编码序列基因突变;免疫组织化学SP法观察蜡块包埋的鼻咽癌组织和癌旁组织中PTEN蛋白的表达情况。免疫印迹法检测PTEN及相关蛋白在细胞株中的表达。结果仅1例鼻咽癌组织检测到PTEN基因第8外显子中存在点突变,但属于沉默突变。71例鼻咽癌组织中PTEN蛋白的表达率(30.9%)显著低于癌旁组织(52.1%,P=0.017)。Ⅲ-Ⅳ期肿瘤组织PTEN阳性表达率(25.5%)显著低于Ⅰ-Ⅱ期肿瘤组织(55%,P=0.026)。EB病毒阳性组PTEN蛋白表达率与EB病毒阴性组比较明显降低(P=0.03)。EB病毒潜伏膜蛋白1(LMP1)可以下调PTEN蛋白的表达。结论PTEN蛋白的表达缺失在鼻咽癌的发生、发展过程中起着重要作用,其缺失可能与EB病毒有关。Objective To investigate the mutation and expression of tumor suppression gene phosphatase and tensin homolog deleted on chromosome ten （PTEN） in patients with nasopharyngeal carcinoma. Methods Four nasopharyngeal carcinoma cell lines （CNE-1, CNE-2, HONE1 and S UNE1）, 96 specimens of undifferentiated non-keratinizing nasopharyngeal carcinoma （96 specimens of tumor tissue and 71 specimens of tissue adjacent to tumors were obtained from patients） and 5 specimens of chronic nasopharyngitis were collected. Four nasopharyngeal carcinoma cell lines, 5 chronic nasopharyngitis specimens and 25 nasopharyngeal carcinoma specimens were included in analyzing PTEN mutation. Paraffin-embedded specimens of tumor and tissue adjacent to tumors obtained from other 71 patients with undifferentiated non-keratinizing nasopharyngeal carcinoma were examined by immunohistochemistry for the analysis of PTEN protein expression. Reverse-transcription polymerase chain reaction （RT-PCR） and direct DNA sequencing methods were employed to test PTEN mutations. The SP immunohistochernistry was employed to detect the expression of PTEN protein. Western blotting was used to determine the expression of PTEN and relative proteins. Results Among 4 human nasopharyngeal carcinoma cell lines, 5 normal nasopharyngeal tissues and 25 nasopharyngeal carcinoma tissues, the point mutation in exon 8 was found in only one carcinoma tissue, but it was a silent mutation. The expression of PTEN protein in human nasopharyngeal carcinoma tissues （30. 9%） was significantly lower than that in tissues adjacent to tumors （52. 1%, P=0. 017）. The positive expression of PTEN protein in stage Ⅲ-Ⅳ （25. 5%） was significantly lower than that in stage Ⅰ-Ⅱ （ P=0. 026）. PTEN protein expression in Epstein-Barr virus （EBV）-positive tissue was lower than that in EBV-negative tissues （P=0. 03）. PTEN expression was down-regulated by latent membrane protein 1 （LMP1）. Conclusions Default of PTEN expression, rather than PTEN mutation, p

关 键 词：PTEN蛋白 人 鼻咽肿瘤 突变 基因表达 

分 类 号：R739.6[医药卫生—肿瘤]