Alteration of early growth response 1 expression in gastroenterological cancers and its biological significance

目的 明确早期生长反应因子1(EGRl)在胃癌、肝癌、大肠癌和食管癌中的表达水平变化,探讨其在肿瘤发生发展中的作用.方法 在获得胃癌差异基因表达谱的基础上,利用逆转录聚合酶链反应(RT-PCR)在胃癌组织和癌旁形态学正常组织及非癌患者正常胃黏膜组织中验证EGR1基因mRNA的表达水平;进一步利用RT-PCR和Western印迹分析比较EGR1在20株肿瘤细胞系(胃癌7株、肝癌5株、大肠癌5株及食管癌3株)中mRNA和蛋白水平表达的变化;采用组织芯片和免疫组织化学方法分析EGR1在179例癌组织及159例正常组织中的表达变化及生物学意义.结果 在非癌患者正常胃黏膜组织中EGR1基因呈低水平或阴性表达,而在癌和癌旁形态学正常组织均有较高水平的表达,与胃癌基因表达谱信息一致.在多种肿瘤细胞系和癌组织中及癌旁形态学正常组织中均存在EGR1的高表达.在检测的4种人肿瘤组织和癌旁形态学正常组织中EGR1均主要表达于胞质,其中胃癌及癌旁分别为87%(49/56)和79%(43/54);肝癌及癌旁分别为83%(43/52)和79%(32/42);大肠癌和癌旁分别为78%(41/52)和63%(22/35);食管癌和癌旁分别为79%(15/19)和78%(14/18).EGR1在肿瘤组织和癌旁形态学正常组织均呈现高水平表达,差异无统计学意义(P＞0.05).结论 EGR1在癌和癌旁配对正常组织中以胞质为主高表达而在非癌患者正常组织以胞核为主低表达,EGR1可能与癌变早期的细胞异常增殖相关.Objective To investigate the expression of early growth response 1(EGR1)in gastroenterological cancers and its significance in the pathogenesis.Methods RT-PCR was used to determine the expression of EGR1 in normal gastric mucosa tissues from 20 non-tumor patients,gastroenterological tumor tissues and matched para-cancer tissues normal morphologically.RT-PCR and Western blotting were used to analyze the mRNA and protein expression of EGR1 in 20 cancer cell lines.Immunohistochemistry(IHC)was preformed to measure the expression level of EGR1 protein on tissue microarray ineluding 179 tumors and 159 normal tissues.Results EGR1 was overexpressed in gastric cancer (GC)and its matched adjacent normal tissue(ANT),but not expressed or expressed at a low level in the normal gastric mucesa from the non-tumor patients,which was consistent with the GC gene expression profiling data.Overexpression of EGR1 was seen in the 20 cancer cell lines at both mRNA and protein levels. IHC showed strong positive staining of EGR1 protein in the cytoplasm of both tumor tissues and matched normal tissues and showed negative or weaker nuclear staining in the normal gastric mucosa tissues from non-tumor patients. Overexprossion of EGR1 was detected in 87% (49/56) of the GC tissues and 79%(43/54) of their ANTs ; 83% (43/52) of the hepatocellular carcinoma tissues and 79% (32/42) of their ANTs ; 78% (41/52) of colorectal cancer tissues and 63% (22/35) of their ANTs ; and 79% (15/19) of the squamous cell carcinoma tissues and 78% ( 14/18 ) of their ANTs. Conclusion EGR1 may be correlated with the abnormal proliferation of cells at the early stage of malignant transformation.国家重点基础研究发展计划(973计划); 青海省科技重点课题基金中文核心期刊要目总览(PKU)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)0201384-13898