Serglycin调控TGF-β信号通路诱导EMT促进膀胱癌转移机制研究

膀胱癌是我国的常见恶性肿瘤之一，膀胱癌的转移与复发是病人的主要死因。在前期研究中我们发现膀胱癌中Serglycin的表达上调与远处转移显著相关。因此，本项目拟在此基础上进一步探讨Serglycin在膀胱癌转移中的作用机制：通过RT-qPCR、IHC检测膀胱癌组织中Serglycin的表达，分析其与临床病理特征的相关性；上调或下调膀胱癌细胞的Serglycin表达水平，然后采用MTT、迁移及侵袭实验研究其对细胞增殖、迁移及侵袭活性的影响；构建裸鼠原位膀胱癌模型，研究Serglycin过表达对肿瘤体内生长、侵袭与转移的作用；通过酵母双杂交、免疫共沉淀及基因表达芯片技术分析Serglycin在膀胱癌中的调控通路；通过分子生物学实验验证Serglycin对TGF-β信号通路介导的EMT及膀胱癌侵袭、转移的调控作用。

Bladder cancer is one of the most common malignant cancers in China, metastasis and recurrence are the majour causes of patients's death. Our previous study found that the abnormal expression of Serglycin is associated with invasion and meatastasis of bladder cancer. Based on this finding, we propose to investigate the mechanism of Serglycin in bladder cancer invasion and metastasis.We will use.RT-qPCR and IHC to evaluate the expression of Serglycin in bladder cancerous tissues and assess its association with clinical pathological features. We will up- or down-regulate the expression of Serglycin the in bladder cancer cells, then use MTT, migration and invasion assay to analyze the effect of Serglycin on cell proliferation, migration and invasion in vitro.We will constructe bladder cancer nude-mouse model, and evaluate the effect of Serglycin on tumor growth, invasion and metastasis in vivo.We will use molecular biology experiments to verification Serglycin for TGF-β signaling pathway mediated EMT of bladder cancer invasion and metastasis.