食管鳞癌中clusterin的糖基化修饰和表达定位改变  

Glycosylation and localization of clusterin in esophageal squamous cell carcinoma

作　　者：赵晓航[1] 何洪智[2] 王堃[1] 张自森[3] 滕梁红[4] 周兰萍[2] 刘芳[2] 曲佳[1] 

机构地区：[1]海军总医院海战伤救治研究中心基础研究室,北京100037 [2]中国医学科学院肿瘤医院肿瘤研究所分子肿瘤学国家重点实验室,北京100021 [3]郑州大学肿瘤研究所,郑州450052 [4]北京宣武医院病理科,北京100053

出　　处：《第二军医大学学报》2005年第12期1333-1336,共4页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(30225045;30370713;30428011);国家重点基础研究发展规划项目(2004CB518707)

摘　　要：目的:通过分析clusterin的糖基化翻译后修饰状态和定位改变,探讨clusterin在食管鳞癌发生过程中可能的分子机制。方法:对23例食管鳞癌组织及其配对正常食管上皮标本,采用蛋白去糖基化和免疫印迹方法分析不同clusterin蛋白异构体的糖基化修饰状态;采用免疫组化方法分析食管鳞癌组织clusterin异构体定位改变。结果:通常成熟型clusterin在还原状态下相对分子质量为40 000,是一种糖基化的蛋白质,定位于正常食管上皮基底膜下食管黏膜层的疏松结缔组织中并经食管腺分泌到食管黏膜表面和血浆中。23例食管鳞癌组织中clusterin蛋白糖基化修饰均异常,未成熟的clusterin前体和核型clusterin聚集在癌细胞内,而糖化的成熟型clusterin在食管黏膜基质层减少并消失。结论:食管鳞癌中clusterin蛋白的去糖基化修饰及其定位改变可能与肿瘤发生发展密切相关。Objective：To study the glycosylation of different elusterin isoforms and the alterations of their intracellular localizations in esophageal squamous cell carcinoma （ESCC）, so as to better understand the potential mechanisms of clusterin in tumorigenesis of ESCC. Methods： The glycosylation of clusterin proteins was studied after treated with PGNase-F by Western blot analysis in 23 ESCC specimens and their corresponding adjacent tissues. Immunohistochemical staining was used to visualize the intracellular localization of clusterin proteins. Results.. Mature clusterin, a 40 000 glycosylated protein in SDS-PAGE gel, usually presents in the connective tissues of the lamina propria of esophageal epithelial mucosa, and is secreted by esophageal glands onto the esophageal mucosa and in plasm. The glycosylation of clusterin proteins was abnormal in the 23 ESCC specimens, with the premature clusterin and nuclear clusterin aggregated in the cells and the mature clusterin decreased or disappeared in the stromal layer of esophagus. Conclusion.. The deglycosylation and localization alterations of clusterin in ESSC may be closely associated with the tumorigenesis of ESCC.

关 键 词：食管肿瘤 癌 鳞状细胞 CLUSTERIN 糖基化 

分 类 号：R735.1[医药卫生—肿瘤]