项目名称: HOXB7基因促胃癌转移机制研究
项目编号: No.81502090
项目类型: 青年科学基金项目
立项/批准年度: 2016
项目学科: 医药、卫生
项目作者: 何徐军
作者单位: 杭州医学院
项目金额: 18万元
中文摘要: 我们前期通过基因芯片筛选出一个与胃癌发生及转移密切相关的基因---HOXB7。预实验证明其HOXB7在胃癌组织中表达上调;抑制HOXB7表达能够抑制胃癌细胞增殖、克隆形成、侵袭迁移能力,同时上调Vimentin、下调E-Cadherin表达。但其在胃癌中的功能意义以及促转移作用及分子机制仍有待深入探讨。本项目拟通过一系列细胞实验、动物实验、基因芯片、siRNA干扰、信号通路阻断以及病理组织IHC等实验,研究HOXB7在胃癌中的生物学作用及其促胃癌EMT、血管淋巴管形成的相关下游分子机制和参与其中的相关信号通路,阐明ERK通路在HOXB7促血管和淋巴管形成、EMT现象和侵袭迁移之间的调控作用。体内外实验研究HOXB7促胃癌转移的分子机制,为应用以HOXB7作为胃癌治疗的潜在新靶点,提供有力的科学依据。
中文关键词: 胃肿瘤;HOXB7;转移;上皮间质转化;信号通路
英文摘要: Our preliminary study(Gene Arry Screen) has recognized that HOXB7 is a important gene in gastric cancer metastasis. HOXB7 is over-expression in gastric cancer and decrease its expression in gastric cancer cell can significantly inhibit the proliferation, migration and invasion of gastric cancer cells,and also can up-regulate Vimentin, down-regulate E-Cadherin expression.But the functional significance of HOXB7 gene in gastric cancer and its mechanism of promoting metastasis is remain need to explore in this project.In this project, the stable expression of HOXB7 and RNA interferenced cells are used as a cell model.Using the Trans-well, cell cloning, Gene arry screen,siRNA interference, signal path blocking and histopathologic IHC experiments,to study the effect of HOXB7 gene on gastric cancer invasion and migration ability both in vitro and in vivo. And to research the molecular mechanism and related signaling pathways involved in the downstream,such as ERK pathway in HOXB7 promote gastic cancer metastasis from EMT,blood vessels and lymphatic vessel formation.Those reseach to provide a strong scientific basis for application the HOXB7 as potential new targets of stomach cancer treatment.
英文关键词: gastic cancer;HOXB7;metastasis;EMT;Pathway