PRMT2促进ERα阳性乳腺癌侵袭与转移的机制研究

Epithelial to mesenchymal transition (EMT) is critical for invasion and metastasis of tumor cells, but the regulatory mechanism remains unclear. Understanding the initiating factors and regulatory signaling pathways of EMT has become a crucial issue for the prevention and treatment of breast cancer. Preliminary studies from our laboratory show that PRMT2 may promote the EMT of tumor cells through an estrogen receptor (ERα)-mediated mechanism. In this study, we will use ERα(+) breast cancer cell lines MCF7 and T47D as study models to determine the role of PRMT2 in the EMT of tumor cells and elucidate the molecular mechanism of action. We will determine the effect of PRMT2 expression on EMT and tumorigenicity in nude mice of MCF7 and T47D using gene transfer and miRNA technologies, we will define a direct interaction between PRMT2 and ERα using co-immunoprecipitation (CO-IP) and pull-down assay, and we will also identify the target genes involved in PRMT2-induced EMT using dual luciferase reporter assay and ChIP assay. Our study results will advance the understanding of EMT and its role in the invasion and metastasis of ERα positive breast cancer cells.

上皮-间质细胞转换（EMT）与肿瘤的侵袭转移密切相关，但诱导EMT的机理尚不清楚。因此，研究EMT形成的诱导因子及相关信号传导通路成为当前肿瘤侵袭与转移研究的热点。我们前期的工作提示，上调PRMT2表达可促进ERα介导的EMT形成。本项目拟在前期工作基础上，选用ERα阳性乳腺癌MCF7与T47D细胞为研究对象，采用基因转染与miRNA技术，观察PRMT2高表达或低表达对乳腺癌细胞系EMT及裸鼠成瘤的影响；通过pull-down与免疫共沉淀方法，鉴定PRMT2与ERα的相互作用；采用双报告基因与染色质免疫沉淀技术，分析PRMT2对EMT关键因子的影响；探讨乳腺癌组织中PRMT2的表达与EMT的关系。本项目的顺利完成，将阐明PRMT2在ERα阳性乳腺癌侵袭与转移过程中的分子机制，为揭示EMT在乳腺癌侵袭与转移中的作用和机理提供新的实验依据。

上皮-间质细胞转换（EMT）与肿瘤的侵袭转移密切相关，但诱导EMT的机理尚不清楚。因此，研究EMT形成的诱导因子及相关信号传导通路成为当前肿瘤侵袭与转移研究的热点。我们前期的工作提示，上调PRMT2表达可促进ERα介导的EMT形成。本研究在前期工作基础上，选用ERα阳性乳腺癌MCF7为研究对象，采用基因转染与miRNA技术，观察PRMT2高表达或低表达对乳腺癌细胞系EMT及裸鼠成瘤的影响；通过pull-down与免疫共沉淀方法，鉴定PRMT2与ERα的相互作用；采用双报告基因与染色质免疫沉淀技术，分析PRMT2对EMT关键因子的影响；探讨乳腺癌组织中PRMT2的表达与EMT的关系。本研究的顺利完成，阐明了PRMT2在ERα阳性乳腺癌侵袭与转移过程中的分子机制，为揭示EMT在乳腺癌侵袭与转移中的作用和机理提供新的实验依据。