癌蛋白SET在胃癌中的表达及作用机制研究  

Oncoprotein SET Expression and Its Mechanism in Gastric Cancer

作　　者：刘雪文 刘鹏飞 刘莹 马文静 钦闪闪 张亮 张特 LIU Xue-wen;LIU Peng-fei;LIU Ying;MA Wen-jing;QIN Shan-shan;ZHANG Liang;ZHANG Te(Biomedical Research Institute;School of Biomedical Engineering;School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, China)

机构地区：[1]湖北医药学院生物医药研究院,湖北十堰442000 [2]湖北医药学院基础医学院,湖北十堰442000 [3]湖北医药学院生物医学工程学院,湖北十堰442000

出　　处：《湖北医药学院学报》2017年第5期379-385,共7页Journal of Hubei University of Medicine

基　　金：2014年度国家自然科学基金青年项目(81400157);2016年度湖北省自然科学基金面上项目(2016CFB528)

摘　　要：目的:探讨癌蛋白SET(SE translocation)在胃癌中的作用机制及生物学功能。方法:用Western blot、免疫组化实时荧光定量PCR法检测SET及其下游相关蛋白在胃癌组织及细胞中的表达及活化;siRNA及shRNA在胃癌细胞中敲低SET表达,MTT法检测细胞增殖能力,裸鼠皮下荷瘤模型检测SET对肿瘤发生的影响;Transwell侵袭实验及划痕实验检测细胞转移能力;Western blot及蛋白酶活性实验检测SET下游因子表达及活化。结果:与癌旁组相比,SET表达量在胃癌组织中异常上调。敲低SET后发现细胞增殖、肿瘤生长、集落形成、转移能力降低。SET在胃癌发生和转移中的作用主要通过调节其下游蛋白磷酸酶2A(PP2A)发挥作用。结论:SET抑制PP2A在胃癌增殖和转移中具有重要作用。SET可以作为胃癌的诊断标志物及潜在药物治疗靶点。Objective To investigate the mechanism and biological function of oncoprotein SE translocation（ SET） in gastric cancer（ GC）.Methods The expression of SET in gastric cancer tissues and cells was determined by Western blot,immunohistochemistry and real-time quantitative PCR（ RT-q CR）; siRNA or shRNA was used to knock-down the expression of SET in GC cells,then MTT and clonogenic assay were used to detect cell proliferation. Tumor bearing nude mouse model was used to detect the influence of SET on tumor formation. Transwell and wound healing assay were used to determine cell invasion and migration ability of GC cells. Western blot and PP2 A immunoprecipitation phosphatase assay were used to investigate the expression and activity of SET downstream molecules. Results The expression of SET was abnormally up-regulated in gastric cancer tissues compared with the cancer adjacent tissue. After knockdown of SET,cell proliferation,tumor growth,colony formation and metastasis were decreased. The role of SET in the carcinogenesis and metastasis of gastric cancer mainly depends on the regulation of its downstream protein phosphatase 2 A（ PP2 A）.Conclusion SET-induced inhibition of PP2 A plays an important role in cell proliferation and metastasis of gastric cancer. SET can be used as a marker for the diagnosis of gastric cancer and a potential target for drug therapy.

关 键 词：SET 胃癌 预后 转移 PP2A AKT 

分 类 号：R735.2[医药卫生—肿瘤]