葡萄糖调节蛋白78在小鼠胰腺癌发生演进过程中的表达变化  

Changes in the Expression of Glucose-regulated Protein 78 in the Occurrence and Progression of Pancreatic Cancer in Mouse Models

作　　者：牛哲禹 刘乔飞 王梦一 周立 姚鲁田 廖泉 赵玉沛 

机构地区：[1]中国医学科学院北京协和医院北京协和医院基本外科,北京100730

出　　处：《中国医学科学院学报》2015年第3期259-263,共5页Acta Academiae Medicinae Sinicae

基　　金：国家高技术研究发展计划项目(863项目)(2012AA02A212);国家自然科学基金(81272573)~~

摘　　要：目的探讨葡萄糖调节蛋白78(GRP78)在胰腺癌发生演进过程中的表达及意义。方法通过二甲基苯并蒽(DMBA)胰腺原位包埋建立免疫健全C57BL/6J小鼠慢性胰腺炎、胰腺导管上皮内瘤变(Pan IN)及胰腺癌发生演进模型,采用免疫组织化学技术检测GRP78在胰腺癌发生演进各阶段的表达变化。结果建立60例DMBA包埋模型,其中18例(30%)于观察期间死亡,共获得慢性胰腺炎9例(15%);Pan IN 18例(30%),包括Pan INⅠ5例(8.3%),Pan INⅡ9例(15%),Pan INⅢ4例(6.7%);胰腺癌15例(25%)。免疫组织化学结果显示,胰腺癌组织中GRP78表达显著高于癌旁正常导管细胞(χ2=13.39,P=0.000),胰腺癌及高级别Pan IN中的GRP78表达明显高于低级别Pan IN和慢性胰腺炎组织中的表达(χ2=17.84,P=0.000)。结论 GRP78的表达在胰腺癌各阶段差异显著,与胰腺癌的发生及演变相关。Objective To investigate the changes in the expression of glucose-regulated protein 78（ GRP78） in the occurrence and progression of pancreatic cancer in mouse models. Methods The mouse models of chronic pancreatitis,pancreatic intraepithelial neoplasia（ Pan IN）,and pancreatic cancer were successfully established by dimethyl benzene and anthracene（ DMBA） embedding in situ. GRP78 expression was detected in various stages by immunohistochemistry. Results Of these 60 mouse models,18 mice（ 30%） died during the observation period. Two months after the embedding,the survived mice were sacrificed,and HE staining and IHC staining were performed. Among these mice,9（ 15%） developed chronic pancreatitis; 18（ 30%） had Pan IN [Pan INⅠ,5（ 8. 3%）; Pan IN Ⅱ,9（ 15%）; and Pan IN Ⅲ,4（ 6. 7%） ]; 15（ 25%） developed pancreatic cancer. Immunohistochemistry showed that the expression of GRP78 in pancreatic cancer tissue wassignificantly higher than that in adjacent noncancerous duct cells（ χ2= 13. 39,P = 0. 000）. Also,GRP78 expression in pancreatic cancer tissue and high grade Pan IN was significantly higher than that in low grade Pan IN and chronic pancreatitis（ χ2= 17. 84,P = 0. 000）. Conclusion The expression of GRP78 remarkably differs in different stages of pancreatic cancer and therefore is associated with the occurrence and progression of this disease.

关 键 词：胰腺癌 胰腺上皮内瘤变 葡萄糖调节蛋白78 

分 类 号：R735.9[医药卫生—肿瘤]