TCRP1基因在肺癌恶性转化中的作用及机制研究

项目名称： TCRP1基因在肺癌恶性转化中的作用及机制研究

项目编号： No.81472184

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： 贺智敏

作者单位： 广州医科大学

项目金额： 75万元

中文摘要： TCRP1是本项目组自主克隆的舌癌耐药相关基因。前期研究发现：①TCRP1受c-myc转录激活，在肺癌mRNA和蛋白表达明显高于对照组织；②TCRP1通过Akt磷酸化激活而促NIH3T3细胞体外恶性转化；③TCRP1能与Akt在肺癌细胞结合并促进其磷酸化而激活下游信号分子。为深入探讨TCRP1在肺癌恶性转化、生长增殖及存活中的作用及调控机制，本项目拟首先采用TCRP1与c-myc共转染正常支气管细胞，观察表型和分子变化；其次通过干扰TCRP1、Akt在肺癌细胞的表达观察其恶性表型和分子变化；第三构建Akt结合区缺失的TCRP1突变载体，以野生型为对照转化NIH3T3细胞以识别TCRP1功能活性区；第四通过肺癌组织芯片检测分析TCRP1表达与启动子甲基化、c-myc结合区突变、肺癌临床分期、病理分型、转移及预后的相关关系。上述研究可望阐述TCRP1的癌基因样作用，为肺癌发病机制提供新的证据。

中文关键词： C05_气管；支气管；肺肿瘤；恶性转化；舌癌相关耐药蛋白；信号通路；磷酸化

英文摘要： TCRP1, known as tongue caner resistance-associated gene, was firstly cloned in our research group. Recently, we found TCRP1 is transcriptionally regulated by c-myc and TCRP1 expression in lung cancer tissues is much higher than that in normal lung tissues at both mRNA and protein levels. Moreover, TCRP1 maybe bind to Akt to enhance Akt activation to promote the malignant transformation of NIH3T3 cells in vitro. To further explore the role and mechanism of TCRP1 in the malignant transformation, proliferation and survival of lung cancer, in the present project, we will first investigate the changes of phenotype and related molecular in the TCRP1 and c-myc cotransfected normal bronchial epithelial cells. Then, we will observe the changes of malignant phenotype and molecular in lung cancer cells after TCRP1 or Akt knockdown. The third, we will construct the mutant-TCRP1 with Akt binding motif deletion and investigate the role of mutant-TCRP1 in the malignant transformation of NIH3T3 cells. The fourth, we will analysis the correlation between TCRP1 expression and its promoter methylation, c-myc binding site mutation and clinical characteristics including clinical stage, pathological type, metastasis and prognosis of lung cancer. Through these researches, we aim to clarify the oncogenic role of TCRP1 and provide new clues for the pathogenesis study of lung cancer.

英文关键词： lung cancer;transformation;TCRP1;signal pathway;phosphorylation