Growth-regulated oncogene α (GROα) plays an important role in a wide range of normal and pathological conditions, including inflammation, angiogenesis, wound healing, tumor invasion, and metastasis. Egr-1 is a member of the zinc-finger transcription factor family induced by diverse stimuli, including TNFα. However, the role of Egr-1 in GROα expression was previously unknown. This study shows that Egr-1 directly binds to the GROα promoter and transactivates the GROα gene. Silencing of Egr-1 by expression of Egr-1 siRNA abrogated TNFα-induced GROα transcription. We also found that Egr-1 mediates ERK and JNK MAPK-dependent GROα transcription upon TNFα stimulation. Our findings suggest that Egr-1 may play an important role in tumor development through transactivation of the GROα gene in response to TNFα within the tumor microenvironment.
Keywords: ChIP; Chromatin immunoprecipitation; EBS; EMSA; Egr-1; Egr-1-binding sequence; Electrophoretic mobility shift assay; GROα; Growth-regulated oncogene α; IL; Interleukin; MAPK; Mitogen-activated protein kinase; RT-PCR; Reverse transcription-polymerase chain reaction; TNFα; Transcriptional regulation; Tumor microenvironment; Tumor necrosis factor α; siRNA; small-interfering RNA.
© 2013.