title: Transcriptional regulation of the growth-regulated oncogene α gene by early growth response protein-1 in response to tumor necrosis factor α stimulation.
abstract: 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.
authors.affiliation: Department of Biological Sciences, College of Biological Science and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea; Cancer and Metabolism Institute, Konkuk University, Seoul 143-701, Republic of Korea. Electronic address: shinsy@konkuk.ac.kr.
authors.forename: Soon Young
authors.initials: SY
authors.lastname: Shin
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Yoongho
authors.initials: Y
authors.lastname: Lim
authors.forename: Young Han
authors.initials: YH
authors.lastname: Lee
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D015153:Blotting, Western; D002465:Cell Movement; D054360:Chemokine CXCL1 / Q000235:genetics* / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D054360:Chemokine CXCL1; D051766:Early Growth Response Protein 1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha
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