Periostin在前列腺癌侵袭转移中的作用及机制研究

项目名称： Periostin在前列腺癌侵袭转移中的作用及机制研究

项目编号： No.81202033

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2

项目作者： 孙传玉

作者单位： 复旦大学

项目金额： 23万元

中文摘要： 我们通过前列腺癌的蛋白质组学研究发现Periostin(PN)在前列腺癌中明显上调。通过免疫组化和Western-blot验证表明PN在前列腺癌的细胞外基质高表达。体内外实验进一步证实沉默PN的表达能够抑制前列腺癌细胞的生长、侵袭并促进其凋亡。另外，生物信息学的研究结果提示我们：PN通过激活TGF-β/Smad信号通路，进一步激活下游转录因子SP1调控前列腺癌其他差异表达蛋白。因此本课题拟在上述研究的基础上进一步探讨PN在前列腺癌侵袭和转移过程中的作用及机制。通过上调PN在前列腺癌细胞中的表达，观察对前列腺癌细胞体内外生物学行为及EMT的影响；干预TGF-β/Smad信号通路明确PN诱导EMT的信号转导机制；并通过负向调控PN的表达进一步明确其作用机制。 本课题不仅为有助于明确 PN促进前列腺癌侵袭和转移的作用及机制，而且为PN成为一个新的前列腺癌的生物标记物和干预靶点奠定了基础。

中文关键词： 前列腺癌；侵袭；转移；成果细胞特异性因子-2；上皮间质转化

英文摘要： In our recent study,Periostin（PN）was up-regulated in prostate cancer by the proteomics analysis of prostate cancer. The overexpression of PN in the stroma of PCa was confirmed by Western blotting and immunohistochemical stai ning. Furthermore, our results demonstrated that sliencing PN could inhibit growth,migration and promote apoptosis of LNCap cells in vitro and in vivo.Addit ionally, the results of bioinformatics analysis indicated that PN may regulate other differentially expressed proteins of prostate cancer by binding with integrin receptor and activating the downstream transcription factor: SP1 via TGF-β/Smad signal pathway. So, The effect and mechanism of PN on invasion and metastasis of prostate cancer will be furtherly investigated in this study. The effect of PN on biological behaviour and EMT of prostate cancer in vitro and in vivo will be studied by up-regulating the expression of PN. To identify the mechanism of signal transduction of PN induing EMT by interfering TGF-β/Smad signal pathway.Furtherm ore, to furtherly identify the mechanism of PN by negative regulation of PN. The project not only conduces to understand the effect and mechanism of PN on invasion and metastais of prostate cancer, but also establish the foundation for PN as a new biomarker and a promising target of therapeutical interv

英文关键词： Prostate Cancer；Invasion；Metastasis；Periostin；Epithelial mesenchymal transition