Transcriptional regulation of the growth-regulated oncogene α gene by early growth response protein-1 in response to tumor necrosis factor α stimulation

Growth-regulated oncogene alpha (GRO alpha) 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 TNF alpha. However, the role of Egr-1 in GRO alpha expression was previously unknown. This study shows that Egr-1 directly binds to the GRO alpha promoter and transactivates the GRO alpha gene. Silencing of Egr-1 by expression of Egr-1 siRNA abrogated TNF alpha-induced GRO alpha transcription. We also found that Egr-1 mediates ERK and JNK MAPK-dependent GRO alpha transcription upon TNF alpha stimulation. Our findings suggest that Egr-1 may play an important role in tumor development through transactivation of the GRO alpha gene in response to TNF alpha within the tumor microenvironment. (C) 2013 Elsevier B.V. All rights reserved.