STAT3在细胞有丝分裂及肺上皮细胞癌变中的作用实验研究

项目名称： STAT3在细胞有丝分裂及肺上皮细胞癌变中的作用实验研究

项目编号： No.81201537

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 程昕

作者单位： 中国科学院动物研究所

项目金额： 23万元

中文摘要： STAT3 是信号传导与转录激活因子家族的重要成员。近年来多项研究结果显示, STAT3 在多种肿瘤中组成性激活, 与肿瘤的增殖分化密切相关。但STAT3 在细胞周期尤其是有丝分裂期中的作用鲜有报道。我们实验室前期从鹅不食草中分离出一种高效低毒的小分子化合物6-OAP，发现6-OAP能抑制纺锤体与染色体的结合，导致有丝分裂检验点的持续活化, 引起cyclin B1 在细胞内积累，使肿瘤细胞周期阻滞在有丝分裂期。我们进一步对6-OAP生物素标记,通过蛋白芯片发现与6-OAP与STAT3 相互作用，通过免疫共沉淀发现CDC2可以和STAT3结合。提示我们STAT3可能激活有丝分裂检验点,导致有丝分裂异常，促进肿瘤细胞过度增殖。本课题在此基础上，拟通过过表达/干扰等方法明确STAT3 参与有丝分裂纺锤体组装的过程及分子机制，为探索有丝分裂期异常在肿瘤发生中的作用及寻找癌症治疗的新靶点奠定基础。

中文关键词： STAT3；肿瘤发生；细胞周期；；

英文摘要： Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which is encoded by the STAT3 gene in human. STAT3 can promote oncogenesis by being constitutively activated through various pathways. However, the role of STAT3 in mitosis is largely unknown. In our previous study, we found that a sesquiterpene lactone, 6-O-angeloylplenolin (6-OAP), caused mitotic arrest in lung cancer and multiple myeloma cells through activation of spindle assembly checkpoint (SAC) and blockage of ubiquitiniation and subsequent proteasomal degradation of cyclin B1. By using biotin labeling of 6-OAP and protein chip assay techniques, we found that STAT3 is a direct target of 6-OAP. We also found CDC2 is one of the proteins which can bind STAT3 by using Co-Immunoprecipitation. These results suggest that STAT3 may have a critical role in the regulation of mitosis and SAC, and its abnormal activation may confer proliferation advantage to cancer cells. In this project, we will therefore investigate the role for STAT3 to play in cell division cycle and SAC by transfection of this factor into normal lung epithelial cells and silencing STAT3 in lung cancer cells. We will explore the effects of STAT3 on protein components of SAC, anaphase promoting complex (APC)/CDC20 and cyclin B1.We will dissect STAT3's role in lung

英文关键词： STAT3；pathogenesis；cell cycle；；