DNMT1基因与胃癌RASSF1A基因失活的关系  

Relationship between DNMT1 gene and loss of RASSF1A gene in gastric cancer

作　　者：戴勇[1] 廖爱军[1] 苏琦[2] 陈鳞[1] 童汪霞[1] 肖伟升[1] 贺慧鹏[1] 

机构地区：[1]南华大学第一附属医院消化内科,湖南衡阳421001 [2]南华大学肿瘤研究所,湖南衡阳421001

出　　处：《中国现代医学杂志》2012年第14期38-44,共7页China Journal of Modern Medicine

摘　　要：目的研究胃癌组织及癌旁组织中R ASSF1A表达情况,检测沉默DNMT1基因后胃癌SGC-7901细胞系R ASSF1A基因启动子区甲基化状况及R ASSF1A基因表达。方法逆转录-聚合酶链式反应(reversetranscription polymerase chain reaction,R T-PCR)、免疫组织化学方法检测40例胃癌组织和癌旁组织R ASSF1A基因表达情况;R T-PCR、甲基化特异性聚合酶链反应(methylation specific PCR,MSP)检测5-Aza-CdR、RNA干扰技术沉默DNA甲基转移酶1后SGC-7901细胞后R ASSF1A基因表达及DNA甲基化状态改变。结果胃癌组织RASSF1A基因mRNA及蛋白表达率显著低于癌旁组织,(60%vs100%,P<0.05);不同分化程度、临床分期及有无淋巴结转移的胃癌组织中表达差异有统计学意义(P<0.05);SGC-7901细胞RASSF1A基因表达随5-Aza-CdR浓度和作用时间的增加而增强(P<0.05),沉默DNMT1后R ASSF1A基因重新表达,DNA甲基化状态被逆转。结论 R ASSF1A基因在胃癌组织中存在较高的表达缺失,且与胃癌的临床分期、病理分级及淋巴结转移有关,RASSF1A基因可能在DNMT1基因的调控下发生甲基化,丧失其活性。【Objective】 To investigate the mRNA and protein expression of RAS association domain family protein 1A（RASSF1A） gene in the gastric carcinoma and matched tumor-adjacent tissues,as well as the methylation of RASSF1A gene promoter and subsequent mRNA expression in cultured SGC-7901 gastric cancer cell line underlying inhibition of DNA methyltransferase 1（DNMT1） expression.【Methods】 The mRNA and protein expressions of RASSFlA gene in 40 gastric carcinoma and their matched tumor-adjacent tissues were detected by reverse transcription polymerase chain reaction（RT-PCR） and immunohistochemisty,respectively.After SGC-7901 cells were treated with 5-Aza-CdR and DNMT1 siRNA,the mRNA expressions of RASSF1A and methylation of RASSF1A gene promoter in SGC-7901 cells was detected by reverse transcription polymerase chain reaction（RT-PCR） and methylation-specific PCR,respectively.【Results】 The rate of RASSF1A mRNA and protein expressions was significantly lower in gastric cancer than that in tumor-adjacent tissues（60% vs 100%,P 〈0.05）.In gastric cancer,loss of RASSF1A expression significantly associated with tumor differentiation,clinical stage or lymph node metastasis（P 〈0.05）.In SGC-7901 cells,inhibition of DNMT1 expression by DNMT1 specific inhibitor dose-dependently,or DNMT1 specific siRNA increased RASSF1A expression（P 〈0.05）.【Conclusion】 Loss of RASSF1A expression in gastric cancer is closely associated with the tumor differentiation and progress.DNMT1-mediated methylation of RASSF1A gene promoter might be a reason for the loss of RASSF1A expression in the gastric carcinoma.

关 键 词：胃癌 RASSF1A DNA甲基化 DNMT1 

分 类 号：R735.2[医药卫生—肿瘤]