O-032. The role of early growth response family of transcription factors in male fertility

Abstract Background: Early growth response family members (EGRs), EGR1-4, have increasingly attracted attention in multiple cancers. However, the exact expression patterns and prognostic values of EGRs in the progress of breast cancer (BRCA) remain largely unknown. Methods: The mRNA expression and prognostic characteristics of EGRs were examined by the Cancer Genome Atlas (TCGA), Oncomine and Kaplan-Meier plotter. Enrichment analyses were conducted based on protein-protein interaction (PPI) network. The Tumor Immune Estimation Resource (TIMER) database and MethSurv were further explored. The protein expression level of EGR1 and cell migration were measured by Western blotting, immunohistochemistry, wound-healing assay and Boyden chamber assay in BRCA. Results: The transcriptional levels of EGR1/2/3 displayed significantly low expression in BRCA compared to that in normal tissues, while EGR4 was shown adverse expression pattern. Survival analysis revealed up-regulated EGR1-4 were remarkably associated with favorable relapse-free survival (RFS). A close correlation with specific tumor-infiltrating immune cells (TIICs) and several CpG sites of EGRs were exhibited. Immunohistochemistry assays showed that the protein expression of EGR1 was remarkably downregulated in BRCA compared to that in paracancerous tissues. Cell migration of MCF10A cells was increased after the silence of EGR1 by siRNA transfection.Conclusions: This study provides a novel insight to the role of EGR1 in the prognostic value and cell migration of BRCA.

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Early growth response transcription factors: Key mediators of fibrosis and novel targets for anti-fibrotic therapy

Matrix Biology ◽

10.1016/j.matbio.2011.03.005 ◽

2011 ◽

Vol 30 (4) ◽

pp. 235-242 ◽

Cited By ~ 51

Author(s):

Swati Bhattacharyya ◽

Minghua Wu ◽

Feng Fang ◽

Warren Tourtellotte ◽

Carol Feghali-Bostwick ◽

...

Keyword(s):

Transcription Factors ◽

Growth Response ◽

Early Growth ◽

Early Growth Response ◽

Novel Targets

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The Role of Early Growth Response 1 (EGR1) in Brain Plasticity and Neuropsychiatric Disorders

Frontiers in Behavioral Neuroscience ◽

10.3389/fnbeh.2017.00035 ◽

2017 ◽

Vol 11 ◽

Cited By ~ 89

Author(s):

Florian Duclot ◽

Mohamed Kabbaj

Keyword(s):

Growth Response ◽

Brain Plasticity ◽

Neuropsychiatric Disorders ◽

Early Growth ◽

Early Growth Response ◽

Early Growth Response 1

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The transcription factor early growth response factor-1 (EGR-1) promotes apoptosis of neuroblastoma cells

Biochemical Journal ◽

10.1042/bj20021918 ◽

2003 ◽

Vol 373 (3) ◽

pp. 739-746 ◽

Cited By ~ 39

Author(s):

Miguel PIGNATELLI ◽

Rosario LUNA-MEDINA ◽

Arturo PÉREZ-RENDÓN ◽

Angel SANTOS ◽

Ana PEREZ-CASTILLO

Keyword(s):

Growth Response ◽

P53 Protein ◽

Early Growth ◽

Early Gene ◽

Terminal Deoxynucleotidyl Transferase ◽

Response Factor ◽

P53 Family ◽

Early Growth Response ◽

In Cells

Early growth response factor-1 (EGR-1) is an immediate early gene, which is rapidly activated in quiescent cells by mitogens or in postmitotic neurons after depolarization. EGR-1 has been involved in diverse biological functions such as cell growth, differentiation and apoptosis. Here we report that enforced expression of the EGR-1 gene induces apoptosis, as determined by flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein nick-end labelling (TUNEL) analysis, in murine Neuro2A cells. In accordance with this role of EGR-1 in cell death, antisense oligonucleotides increase cell viability in cells cultured in the absence of serum. This apoptotic activity of the EGR-1 appears to be mediated by p73, a member of the p53 family of proteins, since an increase in the amount of p73 is observed in clones stably expressing the EGR-1 protein. We also observed an increase in the transcriptional activity of the mdm2 promoter in cells overexpressing EGR-1, which is paralleled by a marked decrease in the levels of p53 protein, therefore excluding a role of this protein in mediating EGR-1-induced apoptosis. Our results suggest that EGR-1 is an important factor involved in neuronal apoptosis.

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Ternary Complex Factors Elk-1 and Sap-1a Mediate Growth Hormone-Induced Transcription of Egr-1 (Early Growth Response Factor-1) in 3T3-F442A Preadipocytes

Molecular Endocrinology ◽

10.1210/mend.13.4.0266 ◽

1999 ◽

Vol 13 (4) ◽

pp. 619-631 ◽

Cited By ~ 36

Author(s):

Richard W. E. Clarkson ◽

Catherine A. Shang ◽

Linda K. Levitt ◽

Tammy Howard ◽

Michael J. Waters

Keyword(s):

Transcription Factors ◽

Ternary Complex ◽

Growth Response ◽

Early Growth ◽

Ternary Complexes ◽

Response Factor ◽

Site Specific ◽

Early Growth Response ◽

Ets Factors ◽

Serum Response

Abstract In our search for transcription factors induced by GH, we have analyzed immediate early gene activation in a model of GH-dependent differentiation. Here we describe the activation of early growth response factor-1 (egr-1) in GH-stimulated 3T3-F442A preadipocytes and the transcription factors responsible for its transactivation. Binding activity of egr-1 in electrophoretic mobility shift assay (EMSA) increased transiently 1 h after GH stimulation, accompanied by a concomitant increase in egr-1 mRNA. egr-1 induction appeared not to be related to proliferation since it was amplified in quiescent preadipocytes at a time when cells were refractive to GH-stimulated DNA synthesis. Truncations of the proximal 1 kb of the egr-1 promoter revealed that a 374-bp region (−624 to −250) contributes about 80% of GH inducibility in 3T3-F442A cells and approximately 90% inducibility in CHO-K1 cells. This region contains three juxtaposed SRE (serum response element)/Ets site pairs known to be important for egr-1 activity in response to exogenous stimuli. Site-specific mutations of individual SRE and Ets sites within this region each reduced GH inducibility of the promoter. Use of these site-specific mutations in EMSA showed that disruption of either Ets or SRE sites abrogated ternary complex formation at the composite sites. DNA binding of ternary complexes, but not binary complexes, in EMSA was rapidly and transiently increased by GH. EMSA supershifts indicated these ternary complexes contained serum response factor (SRF) and the Ets factors Elk-1 and Sap-1a. Coexpression of Sap-1a and Elk-1 resulted in a marked increase in GH induction of egr-1 promoter activity, although transfection with expression vectors for either Ets factor alone did not significantly enhance the GH response. We conclude that GH stimulates transcription of egr-1 primarily through activation of these Ets factors at multiple sites on the promoter and that stabilization of ternary complexes with SRF at these sites maximizes this response.

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