ERLIN2促进乳腺癌细胞生长及调控Herceptin耐药性的分子机制研究

项目名称： ERLIN2促进乳腺癌细胞生长及调控Herceptin耐药性的分子机制研究

项目编号： No.81372855

项目类型： 面上项目

立项/批准年度： 2014

项目学科： 医药、卫生

项目作者： 王国慧

作者单位： 郑州大学

项目金额： 70万元

中文摘要： 我们前期研究发现一个新的可能乳腺癌癌基因：ERLIN2。该蛋白是一个内质网跨膜蛋白，在约15%乳腺癌中高表达，同时部分Her2受体阳性，与乳腺癌较差预后有明显相关性。体外实验发现该基因具有促进乳腺癌细胞生长、恶性转化乳腺正常上皮细胞的作用，分子机制是抑制内质网应激引起的UPR信号通路所致的细胞凋亡，进一步研究发现ERLIN2与Herceptin及化疗药耐药性具有一定相关性，因此本课题将进一步从细胞、动物以及患者样本水平深入研究其癌基因特征及耐药调控机制，主要内容如下：1.进一步研究ERLIN2调控乳腺癌细胞及荷瘤裸鼠的生长作用。2. ERLIN2对Her2阳性乳腺癌细胞Herceptin耐药的调控作用。3.ERLIN2调控Herceptin耐药性的分子机制研究。希望通过本课题研究，找到新的乳腺癌生物标志物及个体化治疗新靶点，为将来应用于临床提供理论基础与实验依据。

中文关键词： C21_；乳腺肿瘤;癌基因ERLIN2;细胞生长;herceptin耐药;分子机制

英文摘要： Our Previous analysis from the breast cancer cell line and speciman has led us to identify an endoplasmic reticulum (ER) lipid raft-associated 2 (ERLIN2) gene as one of candidate oncogenes in approximately 15% human breast cancer , particularly in luminal subtype, and is associated with poor prognosis. In our preliminary study, we found that amplification of the ERLIN2 gene and over expression of the ERLIN2 protein are present in both luminal and Her2 subtypes of breast cancer. The gain- and loss-of-function approaches demonstrated that ERLIN2 is a pro-growth factor for the breast cancer cells. The cells grow more quickly with knock-in ERLIN2 and slower with knock-out ERLIN2, and MCF10A cells could be transformed by overexpressing ERLIN2 in virto. And we found that ERLIN2 has a relationship to the Herceptin resistance amd other anticancer agents. So we propose this project to investigate deeply the role of ERLIN2 in breast cancer. Firstly, we will investigate deeply the pro-growth function of ERLIN2 in breast cancer in vivo, in vitro and on the specimen from patients. Secondly, we will investigate the regulating effect of ERLIN2 in the herceptin resistance in some breast cancer subtype in vitor and in vivo . Finally, we will look into throughly the molecular mechanism of ERLIN2 in the herceptin resistance and try to find out the full picture of the upstream and down stream pathway in the resistance to Herceptin treatment. The project will shed new light on understanding the mechanism of breast cancer malignancy and might offer a new promising biomarker and therapy target for breast cancer in the

英文关键词： breast cancer;cancer gene;pro-growth factor;herceptin resistance;molecular mechanism