叶酸受体α在胃癌组织中的表达及其与叶酸、亚甲基四氢叶酸还原酶基因多态性以及胃癌生物学行为的关系  

Expression of Folate Receptor alpha and its Correlation with Folate, Methylenetetrahydrofolate Reductase Gene Polymorphisms and Biological Behaviour of Gastric Cancerous Tissue

作　　者：翁玉蓉[1] 房静远[1] 孙丹凤[1] 陈朝飞[1] 陆嵘[1] 顾伟齐[1] 朱红音[1] 

机构地区：[1]上海交通大学医学院附属仁济医院,上海市消化疾病研究所200001

出　　处：《胃肠病学》2006年第4期198-201,共4页Chinese Journal of Gastroenterology

基　　金：国家自然科学基金项目(No.30470781);上海市科委重大项目(No.04DZ14006);上海市重点学科建设项目(No.Y0205)资助

摘　　要：背景:叶酸缺乏与胃癌发生有关,亚甲基四氢叶酸还原酶(MTHFR)是叶酸代谢途径的关键酶之一,叶酸受体α(FRα)可介导细胞外叶酸进入细胞内。目的:探讨人胃癌组织中FRα的表达及其与叶酸、MTHFR基因多态性以及胃癌生物学行为的关系。方法:收集38例胃癌患者的癌组织、癌旁和外周正常组织标本,以自动化学发光系统测定叶酸含量,以聚合酶链反应(PCR)-限制性片段长度多态性(RFLP)技术检测MTHFR基因677(C→T)和1298(A→C)两个常见多态,并以即时逆转录PCR(real-timeRT-PCR)检测FRα的表达。结果:FRα在胃癌组织中的表达显著降低(P<0.01),且表达降低癌组织与表达无变化癌组织相比,叶酸含量呈降低趋势(P=0.06)。FRα的表达与MTHFR基因多态性无明显相关性。年龄≥60岁、有淋巴结转移以及肿瘤直径≥5cm的胃癌组织FRα表达水平更低(P≤0.05)。结论:胃癌组织中FRα低表达影响了细胞外叶酸进入细胞内,从而参与了胃癌的发生,其表达降低与年龄增长和胃癌的进展有关。Background： Folate deficiency is thought to be associated with gastric carcinogenesis. Methylenetetrahydrofolate reductase （MTHFR） plays a central role in folate metabolism, and folate receptor alpha （FRot） can mediate extracellular folate into the cells. Aims： To appraise the expression of FRα and its correlation with folate, MTHFR gene polymorphisms and biological behaviors of gastric cancerous tissues. Methods： Folate concentration in gastric cancerous tissue from 38 patients with advanced gastric cancer was detected by automated chemiluminescence system. Two common polymorphisms [677 （C→T） and 1298 （A→C）] of MTHFR gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. The mRNA expression of FRα was detected by real-time reverse transcriptase （RT）-PCR. Results- FRot expression was significantly decreased in gastric cancerous tissue （P〈0.01）. Folate concentration was at a declining trend in FRα down-regulated tissues as compared with that of the normal expression ones （P=0.06）. FRα expression was not associated with MTHFR gene polymorphisms. The expression of FRot was even lower in those older than 60 years of age, with positive lymph node metastasis and tumor diameter greater than 5 cm （P〈0.05）. Conclusions： Down-regulation of FRα influences the entrance of folate into the cells of gastric cancerous tissue and thereby involved in carcinogenesis, which is relevant with aging and the development of gastric cancer.

关 键 词：叶酸受体Α 胃肿瘤 叶酸 亚甲基四氢叶酸还原酶 基因多态性 

分 类 号：R735.2[医药卫生—肿瘤]