鼻咽鳞癌组织RASSF1A基因表达失活及其临床意义的探讨  

Epigenetic inactivation and clinical significance of tumor suppressor gene RASSF1A in nasopharyngeal squamous carcinoma tissues

作　　者：刘伟[1] 陈叶珊[1] 姚杰[1] 王涛[1] 

机构地区：[1]华中科技大学附属协和医院肿瘤中心,湖北武汉430022

出　　处：《中华肿瘤防治杂志》2009年第6期424-427,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：湖北省卫生厅基金项目(3-169)

摘　　要：目的:研究鼻咽鳞癌组织中的抑癌基因RASSF1A的表达及其基因启动子区异常甲基化的情况。并分析DNA异常甲基化与鼻咽鳞癌临床病理因素之间的关系。方法:利用RT-PCR和MS-PCR的方法,分析38例鼻咽鳞癌组织标本、10例鼻咽炎性组织标本、4例正常鼻咽黏膜组织标本、两种鼻咽癌细胞株中RASSF1A基因的表达和其基因启动子区异常甲基化的情况。采用甲基化抑制剂5-Aza-CdR处理鼻咽癌细胞株,观察RASSF1A重新表达的情况。结果:38例鼻咽癌组织标本和两种细胞株的RASSF1A基因表达显著低于对照组(P<0.05);71.05%的鼻咽癌标本及两种鼻咽癌细胞株发生异常甲基化;甲基化与年龄、性别、临床分期和颈部淋巴结转移无相关性(P>0.05),与RASSF1A基因表达和肿瘤分化程度有关(P<0.05);用5-Aza-CdR处理的低表达RASSF1A基因的鼻咽癌细胞株,RASSF1A基因表达上调。结论:鼻咽癌患者肿瘤组织中存在RASSFIA基因的表达下调现象,基因转录启动区的异常甲基化是导致鼻咽癌组织中RASSF1A基因表达下调的主要原因。OBJECTIVE：To study the expression of tumor suppressor gene RASSF1A and the status of aberrant promoter hypermethylation of RASSF1A in nasopharyngeal squamous carcinoma, and analyze the correlation between aberrant DNA methylation and clinical pathological factors in NPC. METHODS： RT-PCR and MS-PCR strategies were used for analyzing the status of gene expression and aberrant promoter methylation of RASSF1A in 38 specimens of nasopharyngeal squamous carcinoma tissue, 10 specimens of nasopharyngeal inflammation tissue,4 specimens of normal nasopharyngeal epithelial tissue and two NPC cell lines. To assess the reactivation of RASSF1A expression, A NPC cell lines （CNE-2） was treated by demethylation agent 5-Aza-2′-deoxycytidine. RESULTS：The expression level of RASSF1A was significantly lower in 38 NPC specimens and two cell lines than in control group （P〈0.05）. MS-PCR analysis demonstrated that RASSF1A promoter region hypermethylation was found in 71.05% of NPC samples, and two cell lines. Aberrant promoter hypermethylation of RASSF1A was correlated with the expression level of RASSF1A and the histological type （P〈0.05）, but not with the age, gender, tumor differentiation grade, metastasis and tumor stage （P〉0.05）. The expression level of RASSF1A was of up-regulation in CNE-2 cells after bing treated with 5-Aza-CdR. CONCLUSION： Down-regulated RASSF1A gene expression might be present in the nasopharyngeal carcinoma tissues of NPC patients and might be caused by epigenetic and genetic mechanisms in NPC.

关 键 词：鼻咽肿瘤 基因 肿瘤抑制 基因 ras 基因缺失 甲基化 

分 类 号：R739.63[医药卫生—肿瘤]