PinX1基因通过MT4-MMP调节乳腺癌转移的分子机制研究

项目名称： PinX1基因通过MT4-MMP调节乳腺癌转移的分子机制研究

项目编号： No.81201636

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： 白津

作者单位： 徐州医学院

项目金额： 23万元

中文摘要： 转移是乳腺癌患者死亡主要原因。研究发现，赋予肿瘤细胞突破基底膜能力的膜基质金属蛋白酶（MT-MMP）家族中的MT4-MMP与乳腺癌转移关系密切。PinX1是近年发现的一个重要抑癌基因，该基因在乳腺癌转移中的作用尚不清楚。申请者预实验发现，沉默乳腺癌细胞PinX1基因，可以显著增加MT4-MMP表达，并促进其迁移及侵袭。本课题将对PinX1基因通过MT4-MMP调节乳腺癌转移的分子机制进行研究。 本研究包括：①用745例乳腺癌患者的组织芯片，研究PinX1和MT4-MMP表达与乳腺癌病理、转移和预后的关系，以及PinX1和MT4-MMP表达之间的关系；②构建高、低表达PinX1的乳腺癌细胞模型，研究PinX1在乳腺癌转移中的作用及MT4-MMP参与的分子机制；③用裸鼠模型，验证PinX1在体内的抑癌作用，及其对MT4-MMP的影响。本研究的成功将为乳腺癌的分子诊断和基因治疗提供新的靶点。

中文关键词： PinX1；乳腺癌；转移；预后；NF-κB

英文摘要： Metastasis is the leading cause of death in breast cancer patients. It was found that MT4-MMP as a family member of membrane matrix metalloproteinases (MT-MMP) plays an important role in the process of tumor cell invasion through the basement membrane. PinX1 was found to be a tumor suppressor gene in recent years, but its role in the metastasis of breast cancer is not clear. In our previous study, we found that silencing PinX1 in breast cancer cells can dramatically increase MT4-MMP expression and cell migration and invasion abilities. Therefore, we focus on the molecular mechanism of PinX1 regulates breast cancer metastasis through MT4-MMP. This project includes: ① We will analysis the correlation between the PinX1, MT4-MMP expression and the pathology, metastasis and prognosis of breast cancer patients by 745 cases tissue microarray; ② We will study the molecular mechanism of PinX1 regulates breast cancer metastasis through MT4-MMP by in vitro cell model; ③ We will verify if PinX1 can suppress tumor growth and metastasis through MT4-MMP by in vivo nude mouse model. Our study will show that PinX1 may be an important marker for human breast cancer metastasis and prognosis as well as a potential therapeutic target.

英文关键词： PinX1；breast cancer；metastasis；prognostic；NF-κB