干扰素调节因子3及其可变剪接体在膀胱癌组织中的表达及意义  

The significance of the expression of interferon regulatory factor 3 and its alternative splicing isoforms in bladder cancer

作　　者：李森[1] 喻希[1] 葛鹏[1] 林健[1] 

机构地区：[1]北京大学第一医院泌尿外科北京大学泌尿外科研究所,100034

出　　处：《中华泌尿外科杂志》2014年第2期139-142,共4页Chinese Journal of Urology

基　　金：吴阶平医学基金（WJP-LC-12036）

摘　　要：目的 探讨干扰素调节因子3（IRF-3）及其4种可变剪接体在膀胱癌发生发展中的作用.方法 采用Trizol法提取正常尿路上皮原代细胞、769-P人肾透明细胞癌细胞株、EJ膀胱癌细胞株3种细胞及北京大学第一医院2012年9月至2013年1月诊治的24例膀胱癌患者的膀胱癌和癌旁正常组织总RNA,采用RT-PCR技术对IRF-3及其4种可变剪接体（IRF-3a、-3c、-3d、-3e）表达情况进行检测,并对组织IRF-3 cDNA开放阅读框架进行测序,检测突变点,分析实验数据.结果 正常尿路上皮中IRF-3d未见表达,IRF-3e的表达较769-P、EJ细胞株的表达弱.48例病理标本中,IRF-3、-3a广泛表达,-3a的表达水平与膀胱肿瘤的分期相关（P=0.01）;-3d、-3e呈现出肿瘤特异性表达趋势（P＜0.05）;-3c在膀胱肿瘤中表达也较正常组织广泛,但表达水平与正常组比较差异无统计学意义（P＞0.05）.对IRF-3突变点检测发现有2种氨基酸的变异引起该分子蛋白二级结构发生变化.结论 IRF-3在正常及肿瘤组织中普遍存在表达,但其可变剪接体尤其是IRF-3d、-3e与膀胱肿瘤的发生相关,-3a的表达水平还与膀胱肿瘤的分期相关.Objective To evaluate the role of interferon regulatory factor 3 （IRF-3） and its alternative splicing isoforms in bladder cancer.Methods RNA was isolated from 3 cell lines （normal human urothelium cells,769-P,EJ） and 48 cases of bladder cancer tissues and adjacent normal tissues from Peking university first hospital between Jun.2012 to Jan.2013 by Trlzol method.RT-PCR was used to examine IRF-3 and its four alternative splicing isoforms （IRF-3a,-3c,-3d,-3e）.Sequencing technology was used to find the point mutations in open reading frame of IRF-3 cDNA.Results The expression of IRF-3d is negative in normal human urothelium cells and the level of IRF-3d is lower than that in 769-P and EJ cell lines.In the 48 cases of pathological specimens,IRF-3 and IRF-3a expressed widely and no significant difference was observed between tumor and normal tissues.IRF-3d and-3e showed tumor-specific expression （P＜0.05）.Although IRF-3c expressed more widely in tumor than in normal tissues,no statistical significance was observed.There was a correlation between IRF-3a and bladder tumor staging.Conclusions IRF-3 ubiquitously expressed in tumor and normal tissue （P =0.01）.Its alternative splicing isoforms IRF-3d and-3e had significant correlations with bladder tumor occurrence.IRF-3a expression was also associated with bladder tumor staging.

关 键 词：干扰素调节因子3 可变剪接体 点突变 膀胱癌 

分 类 号：R737.14[医药卫生—肿瘤]