食管鳞状细胞癌中dact1、2、3基因的表达及表观遗传学失活机制的研究

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1、授予单位代码10089学号或申请号20122290HebeiMedicalUniversity硕士学位论文科学学位食管鳞状细胞癌中DACT1�2、3基因的表达及表观遗传学失活机制的研究研究生：周珍导师：董稚明教授郭炜教授专业：病理学与病理生理学二级学院：第四医院2015年3月河北医科大学学位论文使用授权及知识产权归属承诺本学位论文在导师（或指导小组）的指导下，由本人独立完成。本学位论文研究所获得的研究成果，其知识产权归河北医科大学所有。河北医科大学有权对本学位论文进行交流、公幵和使用。凡发表与学位论文主要内容相关的论文，第一署名单位为河北医科大学，试验材料、原始数据、申报的专利等知识

2、产权均归河北医科大学所有。否则，承担相应的法律责河北医科大学研究生学位论文独创性声明本论文是在导师指导下进行的研究工作及取得的研究成果，除了文中特别加以标注等内容外，文中不包含其他人己发表或撰写的研究成果，指导教师对此进行了审定。本论文由本人独立撰写，文责自负。研究生签名:导师签章^J年3月P日目录中文摘要·················································································1英文摘要·······················································

3、··························5英文缩写···············································································10研究论文食管鳞状细胞癌中DACT1、2、3基因的表达及表观遗传学失活机制的研究前言·····································································11材料与方法··························································12结果····

4、································································18附图····································································22附表·································································27讨论·····································································33结论·············

5、························································36参考文献························································37综述DACT基因在肿瘤中的研究进展·········································40致谢···········································································48个人简历································

6、·····································49中文摘要食管鳞状细胞癌中DACT1、2、3基因的表达及表观遗传学失活机制的研究摘要目的：食管癌是常见且致死性较高的癌症之一。食管鳞状细胞癌是食管癌的主要类型。吸烟、多红肉饮食、较低社会经济状态等都与食管鳞状细胞癌的高发有关。近年来尽管在食管鳞状细胞癌的治疗方面有了一些进步，但食管鳞状细胞癌病人的整体生存率仍没有明显提高。表观遗传学机制是基因组学和蛋白质组学的纽带。DNA甲基化是目前研究最深入的一项表观遗传学调控机制，其重要性主要体现在恶性肿瘤的早期诊断及判断肿瘤患者预后。DAPPER家族包含三个基因：DAC

7、T1、DACT2和DACT3。人类DACT1、2、3基因分别由799、774、610个氨基酸残基组成，并分别定位于人类染色体的14q22.3、6q27、19q13.32。序列检索发现，DACT1、2、3基因启动子区分别存在2个、1个、5个CpG岛，由此推测DACT1、2、3基因可能也存在甲基化修饰的现象。本研究以四株食管癌细胞系和52例食管鳞状细胞癌患者的癌组织及相应癌旁组织作为标本，分别检测了DACT1、2、3基因在食管癌细胞系及肿瘤组织中的甲基化状态及