基底型乳腺癌干细胞信号传导网络结构建模

项目名称： 基底型乳腺癌干细胞信号传导网络结构建模

项目编号： No.31471251

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 戴晓峰

作者单位： 江南大学

项目金额： 80万元

中文摘要： 基底型乳腺癌具有三阴性特征（ER-、PR-、HER2-），患者预后差，缺少有效治疗药物，目前是乳腺癌研究领域的热点与难点。基底型乳腺癌具有许多肿瘤干细胞特征，在一定程度上是通过破坏机体免疫系统来诱发肿瘤的。因此，揭示癌细胞中肿瘤干细胞的信号传导通路，搞清楚其与免疫应答之间的关联对于探索基底型乳腺癌的有效治疗方法至关重要。BRCA1缺陷型肿瘤属于基底型乳腺癌，为研究基底型乳腺癌的发生发展提供了一个良好平台。乳腺癌细胞系与其原始肿瘤具有高度相似的异源性，是我们研究肿瘤的模式系统。本项目旨在利用目前仅有的四个BRCA1突变乳腺癌细胞系HCC1937、SUM149PT、MDAMB436、SUM1315MO2 研究基底型肿瘤中癌症干细胞信号传导通路及其与免疫系统的关联，然后对癌症干细胞信号传导网络结构进行数学建模。该项目的完成是生物实验与生物信息的完美结合，将大大推动我们对基底型乳腺癌的研究进程。

中文关键词： BRCA1突变；基底型乳腺癌；癌症干细胞；生物信息；数学建模

英文摘要： Basal breast cancer is the most deleterious breast tumor subtype, associated with poor overall survival and younger patient age. As it harbors triple negative properties, i.e., lack of estrogen receptor, progesterone receptor and human growth factor receptor 2, no effective treatment is so far available, and thus has attracted lots of attention. Basal breast tumor has many properties of cancer stem cell, which may initiate tumor and foster its growth at least in part via attenuating anti-tumor immune response. Thus, there is an imperative urge for unveiling cancer stem cell signaling and its association with immune response in tumor cells. BRCA1 deficient tumor belongs to basal breast cancer and harbors many sporadic properties. Evidences show that breast cancer cell line displays the same heterogeneity and carries almost all the recurrent genomic abnormalities as the primary tumors. Thus, BRCA1 deficient cell lines offer us a perfect system for investigating the initiation and development of sporadic basal breast cancer. This project aims at utilizing the four current available BRCA1 mutant breast cancer cell lines, i.e., HCC1937, SUM149PT, MDAMB436 and SUM1315MO2 to study cancer stem cell signaling and its associations with immunity. The accomplishment of this project is a demonstration of the power of coherently flowing information between bioinformatics and bench work in cancer research, and will greatly accelerate the progress of finding efficient therapeutic strategies of treating basal breast cancer.

英文关键词： BRCA1 mutation;Basal breast cancer;Cancer stem cell;Bioinformatics;Mathematic Modeling