中文摘要：

目的探究胶质瘤中β—catenin／Tcf-4转录调控AKT2基因以促进其恶性表型转化的机制。方法CHIP—PCR及荧光素酶实验确立AKT2启动子区的Tcf-4结合位点及活性。阿司匹林（ASA）阻断13-catenin／Tcf-4转录复合物活性及恢复AKT2基因的表达后，流式细胞术检测细胞周期，AnnexinV检测凋亡及Transwell实验检测侵袭能力。结果CHIP—PCR表明，AKT2基因启动子区存在两个Tcf-4结合位点-349／-343bp（位点1）和-3491／-3497bp（位点2）。荧光素酶实验结果显示位点2的活性比位点1的强。抑制β—catenin／Tcf-4转录活性后，细胞周期阻滞于G0／G1期，侵袭能力下降；恢复AKT2的表达后，细胞S期比例增加，侵袭能力增强。结论β—catenin／Tcf-4可以直接转录调控AKT2来促进胶质瘤细胞的增殖和侵袭。

英文摘要：

Objective To find out the mechanism of β -catenin/Tcf- 4 transcriptinal regulating AKT2 gene expression in promotion of malignant transformation in human glioma cells. Methods Using CHIP assay and luciferase reporter assays to find out whether β -cateninfTcf- 4 complex could bind to the promoter region of the AKT2 gene directly and the exactly binding site. The AKT2 gene expression was up - regulate after blocking β - catenin /Tcf - 4 activity by ASA. Then flow cytometry, transwell assay, and Annexin V staining were used to evaluate the biological activity of glioma cells. Results CHIP - PCR showed that the promoter region of AKT2 might have two binding sites of Tel - 4. They were located at - 349/-343 bp （binding site 1 ） and -3491/-3497 bp （binding site 2 ） at the transcriptional level. The luciferase reporter assays showed that the luciferase activity of wild type group 2 was stronger than that of wild type group 1. The AKT2 gene could accelerate the proliferation and invasion. Conclusions There are two binding sites of Tel - 4 in the promoter region of AKT2, and the binding site 2 is the main active binding site, located at -3491/- 3497 bp at the transcriptional level. AKT2 plays an important role in promoting proliferation and invasion in β - catenin/Tcf - 4 signal pathway in glioma cells.