HER2/ERK/MAPK通路在恶性脑膜瘤生长、侵袭中的作用研究

Meningiomas are the second most common type of tumour of the central nervous system. Nearly 10% meningiomas may regrow after complete resection，which turns out a poor prognosis.Our previous researches have shown that :1. Her2/neu gene amplification exists in meningiomas.2. A higher tumor grade and recurrence of meningiomas are correlated with a higher rate of HER2 and proliferation. 3. Her2 /neu gene probably plays an important role in the cells proliferation of meningioma. However, the exact mechanism is unknown..This project plans to obtain Her2-transfection malignant meningioma cell line by vector construction and cell transfection mathods etc. And we will use the cell line to detect the expression of some key factors (JNK,ERK5,ERK, p38,etc) in Ras/MAPK pathway by western blot etc.After Corresponding blockers ,we also measure the change of proteins.Furthermore, Edu，TUNEL,Boyden chamber and a tumor formation test in nude mice in vivo will be used to detect the proliferation，apoptosis，and invasion ability. Through researching the molecular biological mechanism about Her2/neu in promoting cell growth and aggressivity of meningiomas,we aim to understand the occurrence and progression in meningiomas,and to provide important experiment data for new clinical individual therapy ,which has an important role in reducing recurrence rate,mortality and improving prognosis for patients with meningioma.

脑膜瘤是颅内第二大常见肿瘤，约10%患者易复发，治疗效果欠佳。前期研究提示：1、脑膜瘤组织中存在Her2/neu基因的扩增；2、细胞增殖活性及HER2与脑膜瘤分级、复发密切相关；3、Her2/neu基因可能参与促进脑膜瘤细胞的增殖。但该基因参与脑膜瘤增殖的具体机制仍不详。本课题拟采用载体构建、细胞转染等方法获取Her2/neu转染及沉默的恶性脑膜瘤细胞株，通过Edu、TUENL、裸鼠体内成瘤实验、Boyden小室法等方法检测转染细胞的增殖、凋亡及侵袭力改变，并运用Western Blot等方法检测Ras/MAPK通路中关键因子JNK、ERK5、ERK和p38的表达情况，以及相应阻断剂作用后各蛋白的变化；进一步探讨Her2/neu是否参与促进恶性脑膜瘤细胞生长、侵袭及其生物学机制，加深对脑膜瘤进展、复发机制的认识，为开辟脑膜瘤个体化治疗提供实验依据，对降低复发率和死亡率、改善预后具有重要意义

脑膜瘤是颅内第二大常见肿瘤，约10%患者易复发，治疗效果欠佳。前期研究提示：1、脑膜瘤组织中存在Her2基因的扩增；2、细胞增殖活性及Her2与脑膜瘤分级、复发密切相关；3、Her2基因可能参与促进脑膜瘤细胞的增殖。但该基因参与脑膜瘤增殖的具体机制仍不详。本课题主要研究内容： 通过体内外实验研究恶性脑膜瘤细胞株沉默和过表达Her2后，细胞增殖、侵袭、迁移情况及细胞周期、凋亡变化情况，同时探讨Her2是否通过ERK/MAPK信号通路影响脑膜瘤的生物学行为。结果：Her2促进脑膜瘤的增殖、侵袭和转移；通过影响细胞周期中G0/G1期向S期进展，促进细胞增殖、抑制凋亡；可能通过调节ERK/MAPK信号通路中ERK5、JNK、ERK1/2、Ras蛋白表达水平而发挥作用。本研究对加深脑膜瘤进展、复发机制的认识，为开辟脑膜瘤个体化治疗提供实验依据，对降低复发率和死亡率、改善预后具有重要意义。