PEA3 activates CXCR4 transcription in MDA-MB-231 and MCF7 breast cancer cells.

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.