Ecotropic viral integration site 1 regulates EGFR transcription in glioblastoma cells

Abstract

AbstractPurposeEcotropic viral integration site-1 (EVI1) is a transcription factor that contributes to the unfavorable prognosis of leukemia, some epithelial cancers, and glial tumors. However, the biological function of EVI1 in glioblastoma multiforme (GBM) remains unclear. Based on microarray experiments, EVI1 has been reported to regulate epidermal growth factor receptor (EGFR) transcription. Signal transduction via EGFR plays an essential role in glioblastoma. Therefore, we performed this study to clarify the importance ofEVI1in GBM by focusing on the regulatory mechanism between EVI1 andEGFRtranscription.MethodsWe performed immunohistochemical staining and analyzed the EVI1-expression in glioma tissue. To determine the relationship betweenEVI1andEGFR, we induced siRNA-mediated knockdown ofEVI1in GBM cell lines. To investigate the region that was essential for the EVI1 regulation ofEGFRexpression, we conducted promoter reporter assays. We performed WST-8 assay to investigate whether EVI1 affected on the proliferation of GBM cells or not.ResultsIt was observed that 22% of GBM tissues had over 33% of tumor cells expressing EVI1, whereas no lower-grade glioma tissue had over 33% by immunohistochemistry. In A172 and YKG1 cells, the expression levels of EGFR and EVI1 correlated. Analysis of theEGFRpromoter region revealed that the EGFR promoter (from − 377 to − 266 bp) was essential for the EVI regulation ofEGFRexpression. We showed that EVI1 influenced the proliferation of A172 and YKG1 cells.ConclusionThis is the first study reporting the regulation ofEGFRtranscription by EVI1 in GBM cells.