BRG1在肺癌组织和肿瘤细胞系中表达下调原因初探  

Preliminary Study on the Cause of BRG1 Down-Expression in Primary Lung Cancers and Multiple Tumor Cell Lines

作　　者：关勇军[1] 蔡秀梅[1] 李友军[1] 何春梅[1] 陈主初[1] 

机构地区：[1]中南大学肿瘤研究所,中国湖南长沙410078

出　　处：《生命科学研究》2007年第2期153-157,共5页Life Science Research

基　　金：国家自然科学基金资助项目(30000074);国家自然科学基金资助项目(30471954)

摘　　要：前期的研究表明:在肺癌及多种肿瘤细胞系中,BRG1(brahma-related gene 1)的mRNA和蛋白质表达下调或缺失,但影响BRG1表达下调的原因并不清楚.因此,用PCR-SSCP(single strand conformation polymor-phism)方法检测18例肺癌组织和15株肿瘤细胞系DNA,并经测序证实:其中有1例肺癌组织的BRG1外显子25第3590位碱基存在T→C的点突变,其编码的BRG1蛋白第1171位氨基酸相应地由Val(缬氨酸)→Ala(丙氨酸),该突变位于BRG1蛋白最重要的功能区(依赖DNA的ATP酶区),提示BRG1突变在肺癌发生中可能起一定的作用.同时,对未检测到BRG1mRNA表达的6例肺癌组织和9株肿瘤细胞系还进行了DNA甲基化分析,结果发现:这些肺癌组织和肿瘤细胞系中BRG1启动子区均无异常甲基化.这说明BRG1在肺癌中表达下调的机制尚需进一步研究.Previous studies have shown the down-expression or loss of BRG1 （brahma-related gene 1 ）protein in primary lung cancers and multiple tumor cell lines,but the cause of BRG1 down-expression in lung cancer remains unknown. So, lung cancer tissues and some tumor cell lines for the mutation of BRG1 by PCR- SSCP （single strand conformation polymorphism） were screened. A point mutation in the exon 25 of BRG1 （base 3590 T→C or amino acid 1171 Val→Ala）was found in a lung tumor sample. This mutation was located in DNA-dependent ATPase domain,the most important domain of BRG1 protein. By the way, no aberrant methylation was detected in the promoter region of BRG1 from 6 primary lung cancers and 9 tumor cell lines that had been demonstrated no expression of the BRG1 mRNA. The down-expression of BRG1 in lung cancer may be caused by other mechanisms, and need further investigation.

关 键 词：BRG1 肺癌 突变检测 甲基化分析 

分 类 号：R730[医药卫生—肿瘤]