UGT1A基因亚族在结肠粘膜及肝组织中的表达  

Expression of UDP-glucuronosyltransferase UGT1A gene in human colon mucosa and liver tissue

作　　者：王敏[1] 孙德峰 李延青[3] 陈建[3] 汪治敏[3] 许晓群[4] 袁孟彪[3] 

机构地区：[1]山东大学齐鲁医院老年病科,山东济南250012 [2]烟台市护士学校遗传学教研室,山东烟台264000 [3]山东大学齐鲁医院消化内科,山东济南250012 [4]山东省医学科学院肿瘤免疫与基因工程重点实验室,山东济南250062

出　　处：《山东大学学报（医学版）》2006年第2期154-160,共7页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金资助项目(30370634/C03030204);山东省保健医学科研课题项目

摘　　要：目的:从mRNA水平及蛋白质水平分析葡萄糖醛酸转移酶UGT1A基因位点在结肠粘膜及肝组织中的表达。方法:结肠癌病例组25例,正常人肠道粘膜20例、正常肝组织12例。用逆转录聚合酶链反应分析结肠癌组、正常人肠道粘膜、肝组织中UGT1AmRNA的表达;用免疫印迹检测各组UGT1A蛋白的表达;用间接免疫荧光技术分析UGT1A蛋白的荧光定位及表达强度。结果:结肠癌组织中UGT1AmRNA表达低于其周围正常粘膜,而后者低于正常人肠粘膜的表达量,正常人群结肠粘膜中,UGT1AmRNA表达总体低于肝组织,P<0.01。结肠癌组、正常人结肠粘膜组织呈现个体差异性表达,而肝脏组织的表达较均质;结肠癌组织、癌周正常粘膜及正常人肠道粘膜中,UGT1A各同工型的表达例数均不相同。UGT1A1、1A3、1A4、1A6、1A9mRNA表达水平在癌组织低于周围正常粘膜,P<0.01,而UGT1A8、1A10在癌组织中mRNA表达量高于周围正常粘膜,P<0.01。肝组织中12例全部均质表达UGT1A1、UGT1A3、UGT1A4、UGT1A6、UGT1A9;UGT1A蛋白灰度比值在结肠癌组织显著低于其周围正常组织,后者又低于正常人肠粘膜,P<0.01。各组内蛋白表达的深浅度亦各不相同,而肝组织的蛋白表达较均质;UGT1A蛋白在结肠定位于粘膜层的上皮细胞,在肝小叶中可见整个肝小叶均质的荧光定位。两种组织的单个细胞内荧光强度等同可比,但单个癌细胞的荧光强度低于正常粘膜上皮细胞。结论:UGT1A基因位点的多态表达不仅存在于结肠癌组织及周围的正常组织,亦存在于正常人群肠粘膜,而肝脏呈均质性表达;结肠粘膜上皮UGT1A基因位点在转录水平及蛋白水平均存在着差异性,不同个体对致癌物的易感性不同可能是这种差异表达的结果。Objective：To analyze the expression pattern of the UDP-glucuronosyhransferase UGTIA gene locus in human colon mucosa and liver tissue. Methods： Colonic epithelium samples from 25 patients with colonic cancer and 20 normal human, and 12 normal liver tissue samples were obtained. UGT1A transcriptions were performed by RT-PCR, and exon-1 specific RT-PCR and UGT1A proteins were detected by Western blotting analysis; meanwhile UGTIA protein in situ was detected by indirect inlnlunofluorescence analysis. Results： UGT1A mRNA expressions were significantly down-regulated in colonic： cancer tissues compared with the smwounding healthy tissues （P〈0.01）, while they were lower in the latter than in normal colonic tissues （P〈0.01）. Colonic UGT1A gene expressions were characterized by significant individual variation,whereas hepatic UGTIA mRNA expressions were more uniform. UGTI A 1,1A3,1A4,1A6,1A9 mRNA levels were differentially down-regulated in the colonic tumor tissues compared with surrounding normal mucosa （P〈0.01）, whereas, UGT1A8 and UGT1A10 mRNA levels were up-regulated compared with the colonic tissues of normal persons. The analysis of pairs of tumor tissues and the surrounding healthy tissues demonstrated lower levels of overall UGT1A protein in the colonic tumor tissue （P〈0.01）; UGT1A immunoiluorescence was localized only in the epithelial cells of the colonic mucosa and was observed throughout the lobulus in liver homogeneous staining.The staining of the individual cancer cell was lower than that of the normal colon epithelium cell. Conclusions： Polymorphic expressions of UGTIA gene locus are presented in both turn（n lissues and the surrounding healthy tissues, as well as in colonic tissues of normal persons, whereas polymorphism UGTIA expression is not presented in human liver. These data provide evidence for the polymorphic regulation and interindividual variation of UGT1A gene locus at the RNA transcript and at the protein level in colonic epithelium, impling that the regula

关 键 词：结肠肿瘤 肝 葡糖醛酸基转移酶 基因 UGT 基因表达 

分 类 号：R735.35[医药卫生—肿瘤] Q786[医药卫生—临床医学]