Department of Breast Surgery, Breast Cancer Institute, Department of Oncology, Shanghai Medical College, Institute of Biomedical Science, Fudan University, China.
Acta Biochim Biophys Sin (Shanghai). 2011 Oct;43(10):771-8. doi: 10.1093/abbs/gmr070. Epub 2011 Aug 10.
CXC chemokine receptor 4 (CXCR4) is a cell surface receptor that has been shown to mediate the metastasis of many solid tumors including lung, breast, kidney, and prostate tumors. In this study, we found that overexpression of ets variant gene 4 (PEA3) could elevate CXCR4 mRNA level and CXCR4 promoter activity in human MDA-MB-231 and MCF-7 breast cancer cells. PEA3 promoted CXCR4 expression and breast cancer metastasis. Chromatin immunoprecipitation assay demonstrated that PEA3 could bind to the CXCR4 promoter in the cells transfected with PEA3 expression vector. PEA3 siRNA attenuated CXCR4 promoter activity and the binding of PEA3 to the CXCR4 promoter in MDA-MB-231 and MCF-7 cells. These results indicated that PEA3 could activate CXCR4 promoter transcription and promote breast cancer metastasis.
细胞外信号调节激酶 4（CXCR4）是一种细胞表面受体，已被证实能介导许多实体瘤的转移，包括肺癌、乳腺癌、肾癌和前列腺癌。在这项研究中，我们发现 ETS 变异基因 4（PEA3）的过表达可使人类 MDA-MB-231 和 MCF-7 乳腺癌细胞中的 CXCR4 mRNA 水平和 CXCR4 启动子活性升高。PEA3 促进了 CXCR4 的表达和乳腺癌的转移。染色质免疫沉淀实验表明，PEA3 可与转染 PEA3 表达载体的细胞中的 CXCR4 启动子结合。PEA3 siRNA 降低了 CXCR4 启动子活性和 PEA3 与 MDA-MB-231 和 MCF-7 细胞中 CXCR4 启动子的结合。这些结果表明，PEA3 可以激活 CXCR4 启动子转录并促进乳腺癌转移。
