Cox-2高表达是肿瘤发生发展的风向指标，深入研究Cox-2调控机制非常必要。预实验中我们采用新的启动子结合蛋白垂钓鉴定系统，成功垂钓出Cox-2调控因子TFAP2B；并发现 乳腺癌细胞中TFAP2B特异性地结合Cox-2启动子，激活其转录活性，影响细胞生长和凋亡。但TFAP2B在调控Cox-2及乳腺癌发生发展中具体的作用和机制及临床意义，尚不清楚。为此，本项目拟过表达或敲低TFAP2B基因，在细胞及动物模型中，进一步研究TFAP2B对Cox-2表达，细胞生长和凋亡、肿瘤形成、以及相关信号通路的影响，进而明确TFAP2B的生物学功能和分子机制。另外，采用组织芯片等技术，分析TFAP2B和Cox-2在乳腺癌组织中的表达，并结合临床资料评估其与乳腺癌分期、生存、转移、复发等的相关性，确定其临床意义。本项目将为揭示乳腺癌发生发展机制提供新认识，也为确立TFAP2B作为肿瘤治疗新靶点提供理论依据。

Cox-2 is the hallmarker of tumorigenesis.It is necessary to discover and identify novel regulatory mechanisms of Cox-2.In the earlier studies, we used a novel system to pull down and identify promoter-binding proteins and found that in breast cancer cells TFAP2B tumor-specifically binds to Cox-2 promoter, activates its transcriptional activity, and affects tumor cell growth and apoptosis. However, the action mechanisms by which TFAP2B regulates Cox-2　and breast cancer growth and development as well as its clinical implications remain unclear. In this study, we will overexpress and knockdown TFAP2B gene to further study the effects of TFAP2B on Cox-2 expression,cell growth and apoptosis, tumor formation, and the signaling pathway involving in tumor development and progression in cell and animal models, thereby identifying the biological functions and molecular mechanisms of TFAP2B. Moreover, we will also analyze TFAP2B and Cox-2 expression in tumor tissues by tissue array and evaluate correlation of TFAP2B with breast cancer stage, survival,metastasis, recurrence by combining the clinical data, thereby identifying the clinical implications of TFAP2B.This program will provide new understanding for identification of the mechanisms of breast cancer development and progression, and provide theoretical and experimental basis for the development of TFAP2B as a new therepeutic target for cancers.