目前研究发现ErbB受体及其突变体在胶质瘤中的过表达与肿瘤放疗耐受性呈正相关，LRIG1基因通过引起ErbB受体泛素化降解对其起到负性调节作用，从而产生抗肿瘤作用。我们前期研究发现干扰LRIG1基因在GL15胶质瘤细胞表达后，GL15胶质瘤细胞的生物学行为明显增强，EGFR的表达水平明显升高，据此推测LRIG1基因可能通过负性调控ErbB受体信号系统及下游成员活性，从而影响脑胶质瘤的放疗耐受性。本课题先从人脑胶质瘤组织标本上研究LRIG1和ErbB基因RNA及蛋白的表达水平及与患者预后的相关性，再通过基因过表达和RNA干扰技术建立过表达和低表达LRIG1的胶质瘤细胞系和相应胶质瘤动物模型并予以X线照射处理，探讨LRIG1基因通过负性调控EGFR信号通路对胶质瘤放疗耐受性的影响及调控机制，为探索胶质瘤放疗耐受性的新机制和胶质瘤治疗新策略提供实验基础和理论依据。

There is evidence showing positive correlation between over expression of epidermal growth factor receptor and its mutant and tumor cell radiation resistance in human glioma. The reason of the anti-tumor effect of LRIG1 gene is that LRIG1 gene negatively regulated epidermal growth factor receptor in human glioma cells, leading to ubiquitin-mediated degradation of epidermal growth factor receptor. Our previous studies have found that down-regulation of LRIG1 expression by RNA interference increases glioblastoma cell (GL15) biological behavior and EGFR expression in vitro. We hypothesize that LRIG1 gene can affect the human glioma radiation resistance. The potential mechanism is that LRIG1 gene negatively regulates the activity of ErbB receptor signaling system and the downstream members. This project aimed to further study the relationship at the RNA and protein levels between the expression of LRIG1 and glioma radiation resistance and the prognosis of patients by using the clinical glioma samples. These in vivo studies will establish the clinical basis. Next, using gene over-expression and RNAi methods, we will study the effect of over expression of ErbB receptor on LRIG1 in glioma cells. Then, cell line and animal experiments will be applied in vitro to study on mechanism of the effect of LRIG1 on glioma radiation resistance by negatively regulating EGFR signal pathway . All of these studies will explore the novel mechanism of radiation resistance in glioma and provide therapeutic strategies for glioma.