Tob基因在大肠癌发生发展中的调控机制研究

项目名称： Tob基因在大肠癌发生发展中的调控机制研究

项目编号： No.81472568

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 胡天惠

作者单位： 厦门大学

项目金额： 72万元

中文摘要： 近期研究发现Tob基因有抗增殖作用，在多种癌症中表达缺失。然而我们观察到Tob在肠癌组织中表达增高，促进肠癌细胞增殖，在肠癌模型鼠APCmin/+肠息肉中表达升高且APCmin/+小鼠与Tob敲除鼠杂交后息肉恶性度降低，提示Tob促进肠癌发生发展，但机制未知。我们拟先通过改变Tob在肠癌细胞中的表达，观察对细胞增殖及转移的影响，并进一步检测Tob与肠癌发生发展密切相关的Wnt和EGFR信号通路的相互影响，探索Tob在肠癌中表达升高及促癌分子机制。动物实验采用APCmin/+小鼠、Tob-/-/ APCmin/+双敲小鼠及AOM+DSS化学诱导肠癌小鼠模型来探讨Tob基因体内动态表达及其在肠癌发生中的作用。临床实验将检测Tob在不同阶段肠癌组织以及术后未复发及复发的切片样本中的表达，推断Tob对肠癌发展及预后的影响。研究力争揭示Tob在肠癌中的调控机制，为肠癌诊治提供分子靶标和理论依据。

中文关键词： 大肠癌；Tob基因；细胞信号转导

英文摘要： Recent studies showed that Tob has the function of anti proliferation and is deficient in many types of cancer. However, we observed raised Tob expression in colon cancer tissues, increased proliferation in Tob overexpressed cancer cells, raised expresssions of Tob in APCmin/+ mice polyps samples, and reduced polyps malignancy in Tob-/-/APCmin/+ mice, indicating that Tob might play roles in induction of colon tumorigenesis. However, the mechanism of Tob in tumorigenesis is largely unknown. We first use overexpression or knock out methods to alter the expression of Tob and study its effect on cell growth, differenciation and migration. Then we studied the correlations between Tob and Wnt and EGFR pathways, which are closely related with colorectal tumorigenesis. In animal experiments we plan to use APCmin/+, Tob-/-/APCmin/+ genetic mouse models plus AOM +DSS chemical models to study the expression and in vivo mechanisms of Tob in the colon tumorigenesis. In clinical studies the expression models of Tob were measured in tissues from different stages of colon cancer. The Tob expressions were also compared between tissues from fifty 6 months recurrence and non-recurrence patients to find out the relatioinship between Tob expression and the progonosis of colon cancers. This study will disclose the mechanisms of Tob in colorectal tumorigenesis and provide insight of Tob related target therapy for colorectal cancers.

英文关键词： colon cancer;Tob gene;cellular signaling