γ-Synuclein调控MAPK-ERK-JNK信号通路及细胞周期促进子宫内膜癌恶性进展的机制研究

项目名称： γ-Synuclein调控MAPK-ERK-JNK信号通路及细胞周期促进子宫内膜癌恶性进展的机制研究

项目编号： No.81460396

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 范余娟

作者单位： 广西医科大学

项目金额： 47万元

中文摘要： γ-神经突触核蛋白（γ-Synuclein）过表达能增加多种肿瘤细胞的侵袭转移能力及化疗耐药性。我们前期发现：子宫内膜癌组织γ-Synuclein表达率明显高于正常内膜组织，并随疾病恶性程度增加而增高，且阳性表达组总体生存率显著低于阴性表达组。但具体机制尚未明确。本研究构建裸鼠人子宫内膜癌宫腔原位移植模型和γ-Synuclein重组慢病毒干扰系统，采用生物信息学、流式细胞术、激光扫描共聚焦显微镜、qRT-PCR、western blot、等技术，经体内、体外实验研究：1.γ-Synuclein高表达与人子宫内膜癌细胞生物学特性的关系；2.γ-Synuclein调控MAPK-ERK-JNK通路活化状态、改变细胞周期促进子宫内膜癌发生发展、浸润转移的作用及机制。对揭示γ-Synuclein在内膜癌作用的新靶点有重要意义，为子宫内膜癌防治尤其对化疗耐药的内膜癌治疗提供新思路。

中文关键词： C23_子宫体肿瘤；γ-Synuclein；MAPK-ERK-JNK信号通路；细胞周期

英文摘要： Overexpression of γ-Synuclein could promote the invasion and metastasis ability also chemoresistance of several kinds of tumour cells. In our preliminary experiment: γ-Synuclein expression rate in endometrial carcinoma was significantly higher than normal endometrium and that increased with the higer degree of malignant disease, what's more, overall survival of positive group was significantly lower than the negative group. But the concrete mechanism was unclear. In this research project, we will structure nude mice intrauterine orthotopic transplantation model and the recombinant lentiviral interference system, using bioinformatics, flow cytometry, laser scanning confocal microscopy, qRT-PCR and western blot to study: 1. The relationship between γ-Synuclein and the biological characterization of human endometrial carcinoma cell lines; 2. The mechanisms of γ-Synuclein regulates MAPK-ERK-JNK signal pathway and cell cycle leading to malignant progression of endometrial carcinoma. The significance of this research will be reveal some new targets of γ-Synuclein gene and also provide some new methods on the prevention and treatment of endometrial cancer especially on that chemotherapy resistant patients.

英文关键词： endometrial cancer;γ-Synuclein;MAPK-ERK-JNK signal pathway;cell cycle