高水平雌激素是I型子宫内膜癌的主要病因，但其具体致病机制不明确。我们在前期研究中发现Nogo-B受体NgBR在I型子宫内膜癌患者的肿瘤组织中表达显著升高，另有研究显示NgBR能够影响Ras在细胞中的定位，基于此，我们提出假设: NgBR通过Ras信号通路介导雌激素对I型子宫内膜癌上皮细胞的促增殖作用，并通过以下实验进行证明：1). 构建NgBR稳定低表达或高表达的子宫内膜癌细胞系，证明雌激素通过刺激NgBR表达影响子宫内膜癌细胞增殖；2）向稳定高表达NgBR细胞系中转染失活的Ras，证明NgBR通过影响Ras活性促进子宫内膜癌细胞增殖；3). 通过细胞移植小鼠肿瘤模型证明NgBR-Ras通路参与对肿瘤生长的调控作用。我们的研究将提出新的子宫内膜癌发病分子机制，为该病的治疗提供新的作用靶点。

The high estrogen levels can promote the progression of the type I endometrial carcinoma（EC）. However, the underlying molecular mechanisms remain unclear. In our previous study, we found that NgBR, the receptor for Nogo-B, is highly expressed in type I EC than normal tissue. It has been reported that NgBR is required for Ras translocation to plasma membrane. Based on the findings above, we hypothesize that the estrogen-enhanced type I EC proliferation might be triggered through NgBR-Ras signaling pathway. Thus, we proposed the following aims in this project, 1) to establish EC cell line with NgBR being stably knocked down or over expression to determine if the estrogen-promoted cell proliferation is dependent on activation of NgBR expression; 2) to transfect NgBR stably over expressed cell line with devitalized Ras to determine if NgBR influences cell proliferation is related to Ras activity; 3)to evaluate the importance of NgBR-Ras pathway in estrogen-activated EC tumor growth in a mouse model. We believe that our project can broaden our understanding on the mechanisms of EC progression, and will provide a new strategy for EC treatment.