转录因子GTF2B对垂体生长激素腺瘤中AIP表达调控及对肿瘤表型影响的分子机制研究

项目名称： 转录因子GTF2B对垂体生长激素腺瘤中AIP表达调控及对肿瘤表型影响的分子机制研究

项目编号： No.81502321

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： 蔡锋

作者单位： 浙江大学

项目金额： 18万元

中文摘要： 芳香烃受体相互作用蛋白(AIP)是垂体生长激素腺瘤(GHPA)中的一类重要抑癌因子。临床观察发现AIP表达水平与GHPA增殖、侵袭、及耐药等表型存在相关性。目前影响AIP表达水平的转录因子调控机制尚未见报道。前期生物信息学分析及预实验结果提示，转录因子GTF2B可与AIP的5’UTR非编码进化保守序列(ncECR)结合，促进AIP转录表达。本项目拟在此基础上，收集临床GHPA标本，并通过动物实验，观察分析GTF2B与AIP表达相关性；利用SH-SY5Y和293T工具细胞，验证GTF2B与AIP5’UTR中ncECR的相互结合作用以及对AIP表达调控的影响；最后，以大鼠GH3细胞为实验细胞，通过体内外实验，验证GTF2B对GHPA增殖、侵袭及耐药等肿瘤表型的影响。本项目旨在揭示GHPA中AIP低表达的转录调控机制，为将来临床治疗此类肿瘤提供思路和前期实验数据。

中文关键词： 垂体生长激素腺瘤；芳香烃受体相互作用蛋白；转录因子；普遍性转录因子IIB；肿瘤表型

英文摘要： Aryl hydrocarbon receptor-interacting protein (AIP) is an important tumor suppressor in GH-secreting pituitary adenoma. Clinically, there is a correlation between the expression of AIP and GHPA phenotype, such as tumor proliferation, invasiveness and drug resistence. Until now, it has not been clear about the mechanism how the expression of AIP is regulated transcriptionally. With the results of bioinformatics analysis and the preliminary experiments, the transcription factor GTF2B is indicated to be able to bind two different non-coding evolutionary conserved regions (ncECR) respectively, and to promote the transcription activity and expression of AIP consequently. Hence, based on these information, first of all, the correlation analysis of expression between AIP and GTF2B is going to be performed, using GHPA samples and xenografts in mice; Then, the combination of the predicted ncECR in AIP 5’UTR and GTF2B will be tested and verified in SH-SY5Y and 293T cells, followed by the research on the effect of it on the expression of AIP and tumor phenotypes in rat GHPA cell line GH3, in vitro and in vivo. It is expected that the transcriptional mechanism about AIP expression in GHPA could be revealed via this study, in order to provide theoretical basis and new therapeutic methods against low AIP-expression GHPA.

英文关键词： GH-secreting pituitary adenoma;aryl hydrocarbon receptor-interacting protein(AIP);transcription factor;GTF2B;tumor phenotype