MTAP在人BEP2D细胞辐射致癌模型和肺癌中表达研究  

Down-regulation of methylthioadenosine phosphorylase in malignant BERP35T-2 cells and in non-small cell lung cancers

作　　者：李邦印[1] 应万涛[2] 戴为民[3] 徐勤枝[2] 霍艳英[2] 胡迎春[2] 张开泰[2] 吴德昌[2] 

机构地区：[1]解放军第三○九医院,北京100091 [2]军事医学科学院放射医学研究所 [3]解放军总医院

出　　处：《中华放射医学与防护杂志》2004年第3期222-225,共4页Chinese Journal of Radiological Medicine and Protection

基　　金：国家重点基础研究发展规划 973基金资助项目(G19980 5 12 0 7)

摘　　要：目的　探索甲硫腺苷磷酸化酶 (MethylthioadenosinePhosphorylase ,MTAP)在人支气管上皮BEP2D永生化细胞的恶性转化过程和临床非小细胞肺癌中的表达变化。方法　培养BEP2D和BERP35T 2细胞 ,制备细胞总蛋白 ,进行双相电泳和质谱分析 ;选择有表达差异的蛋白质点MTAP ,在细胞模型中进行NorthernBlot分析 ;对获得的 15例肺癌标本用RT PCR方法分析验证MTAP的表达水平。结果　双相电泳发现MTAP在恶性转化细胞BERP35T 2中表达降低 ;NorthernBlot分析表明MTAPmRNA在BEP2D永生化细胞中表达水平很高 ,而在BERP35T 2恶转细胞中表达极低 ;对 15例非小细胞肺癌进行RT PCR分析 ,发现MTAP在 73 3% ( 11 15 )的肿瘤组织中低表达 ;在中 低分化组肺癌的低表达频率 ( 90 9% )显著高于高分化组 ( 2 5 % ) ,在腺癌与鳞癌组则没有显著性差异。结论MTAP低表达现象与肺癌恶性转化密切相关 。Objective The aim of this study was to investigate the expression alteration of MTAP gene in tumorgenesis of bronchial epithelial cell line and Chinese non-small lung cancers. Methods Total protein from BEP2D and BERP35T-2 cells was extracted and analyzed by 2-D electrophoesis and peptide mass fingerprinting spectrum.Northern blot was performed to confirm differences of expression of MTAP gene between BEP2D and BERP35T-2.RT-PCR was used to observe the mRNA expression of MTAP in 15 clinical cases with non-small cell lung cancer. Results MTAP was found to be expressed at lower level in malignant BERP35T-2 cells than in BEP2D analyzed by 2-dimensional electrophoresis,which was confirmed at transcriptional level by Northern blot.In 11 out of 15 NSCLC samples analyzed by RT-PCR,MTAP expression was down-regulated.MTAP was poorly expressed in 90 9% of mild/poorly differentiated NSCLC cases,while in 25% of well-differentiated cases. Conclusion The result of this study indicates that the down-regulations of MTAP at protein level or mRNA level in Chinese NSCLC might contribute to the carcinogenesis of lung and MTAP might be a candidate of tumor suppressor gene.

关 键 词：MTAP BEP2D细胞 辐射 致癌模型 肺癌 基因表达 Α粒子 

分 类 号：R734.2[医药卫生—肿瘤]