• 생명과학회지
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• 제31권4호
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• pp.425-429
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• 2021

INS-1 췌장 β 세포에서 Allomyrina dichotoma 혈림프 처리에 의한 early growth response protein 1 (EGR1) 유전자 발현을 조사되었다. 이 연구에서 새로운 발견은 EGR1 유전자 발현을 A. dichotoma 혈림프의 용량 및 시간 의존적으로 상향 조절하는것과 혈림프와 병행한 저체온효과 또는 소포체(endoplasmic reticulum, ER) 스트레스에 의해서도 유전자 발현이 상승하였다. A. dichotoma 혈림프가 EGR1의 유전자발현을 상승 조절을 할 수 있기 때문에, EGR1 관련 질병 치료 및 예방의 실마리를 제공 할 수 있을 가능성을 시사한다.

• 한국발생생물학회지:발생과생식
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• 제18권4호
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• pp.233-240
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• 2014

The early growth response protein 1 (Egr-1) is a widely reported zinc finger protein and a well known transcription factor encoded by the Egr-1 gene, which plays key roles in many aspects of vertebrate embryogenesis and in adult vertebrates. The Egr-1 expression is important in the formation of the gill vascular system in flounders, which develops during the post-hatching phase and is essential for survival during the juvenile period. However, the complete details of Egr-1 expression during embryo development in olive flounder are not available. We assessed the expression patterns of Egr-1 during the early development of olive flounders by using reverse transcription polymerase chain reaction (RT-PCR) analysis. Microscopic observations showed that gill filament formation corresponded with the Egr-1 expression. Thus, we showed that Egr-1 plays a vital role in angiogenesis in the gill filaments during embryogenesis. Further, Egr-1 expression was found to be strong at 5 days after hatching (DAH), in the development of the gill vascular system, and this strong expression level was maintained throughout all the development stages. Our findings have important implications with respect to the biological role of Egr-1 and evolution of the first respiratory blood vessels in the gills of olive flounder. Further studies are required to elucidate the Egr-1-mediated stress response and to decipher the functional role of Egr-1 in developmental stages.

• 대한의생명과학회지
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• 제13권2호
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• pp.157-160
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• 2007

Endoplasmic reticulum (ER) plays formation of disulfide bonds and proper folding of secretory proteins. Cellular responses to ER stress enhances the stress-activated kinase pathway and the induces a lot of immediate-early genes. Among of them, the early growth response-1 (Egr-1), a transcription factor, which plays an important role in cell growth, development, differentiation, apoptosis and various types of injury. For that reason, we have tested the expression of Egr-1 against ER stress inducible drugs (tunicamycin, DTT, A23187 and BFA) to understand what kind of aspect occurred by ER stresses.

• BMB Reports
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• 제53권12호
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• pp.628-633
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• 2020

WNT11 is a member of the non-canonical Wnt family and plays a crucial role in tumor progression. However, the regulatory mechanisms underlying WNT11 expression are unclear. Tumor necrosis factor-alpha (TNFα) is a major inflammatory cytokine produced in the tumor microenvironment and contributes to processes associated with tumor progression, such as tumor invasion and metastasis. By using site-directed mutagenesis and introducing a serial deletion in the 5'-regulatory region of WNT11, we observed that TNFα activates the early growth response 1 (EGR1)-binding sequence (EBS) in the proximal region of WNT11 and that the transcription factor EGR1 is necessary for the TNFα-induced transcription of WNT11. EGR1 bound directly to the EBSs within the proximal 5'-regulatory region of WNT11 and ectopic expression of EGR1 stimulated WNT11 promoter activity, whereas the knockdown of EGR1 expression by RNA interference reduced TNFα-induced WNT11 expression in T47D breast cancer cells. We also observed that mitogen-activated protein kinases (MAPK), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 kinase mediated TNFα-induced transcription of WNT11 via EGR1. Our results suggest that EGR1 directly targets WNT11 in response to TNFα stimulation in breast cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.4137-4142
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• 2015

The zinc finger transcription factor EGR 1 has a role in controlling synaptic plasticity, wound repair, female reproductive capacity, inflammation, growth control, apoptosis and tumor progression. Recent studies mainly focused on its role in growth control and apoptosis, however, little is known about its role in epithelial-mesenchymal transition (EMT). Here, we aim to explore whether EGR 1 is involved in TGF-${\beta}1$-induced EMT in non-smallcell lung cancer cells. Transforming growth factor (TGF)-${\beta}1$ was utilized to induce EMT in this study. Western blotting, RT-PCR, and transwell chambers were used to identify phenotype changes. Western blotting was also used to observe changes of the expression of EGR 1. The lentivirus-mediated EGR 1 vector was used to increase EGR 1 expression. We investigated the change of migration to evaluate the effect of EGR 1 on non-small-cell lung cancer cells migration by transwell chambers. After stimulating with TGF-${\beta}1$, almost all A549 cells and Luca 1 cells (Non-small-cell lung cancer primary cells) changed to mesenchymal phenotype and acquired more migration capabilities. These cells also had lower EGR 1 protein expression. Overexpression of EGR 1 gene with EGR 1 vector could decrease tumor cell migration capabilities significantly after adding TGF-${\beta}1$. These data s howed an important role of EGR 1 in the EMT of non-small-cell lung cancer cells, as well as migration.

• Molecules and Cells
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• 제37권1호
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• pp.24-30
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• 2014

Inductive expression of early growth response 1 (Egr-1) in neurons is associated with many forms of neuronal activity. However, only a few Egr-1 target genes are known in the brain. The results of this study demonstrate that Egr-1 knockout (KO) mice display impaired contextual extinction learning and normal fear acquisition relative to wild-type (WT) control animals. Genome-wide microarray experiments revealed 368 differentially expressed genes in the hippocampus of Egr-1 WT exposed to different phases of a fear conditioning paradigm compared to gene expression profiles in the hippocampus of KO mice. Some of genes, such as serotonin receptor 2C (Htr2c), neuropeptide B (Npb), neuronal PAS domain protein 4 (Npas4), NPY receptor Y1 (Npy1r), fatty acid binding protein 7 (Fabp7), and neuropeptide Y (Npy) are known to regulate processing of fearful memories, and promoter analyses demonstrated that several of these genes contained Egr-1 binding sites. This study provides a useful list of potential Egr-1 target genes which may be regulated during fear memory processing.

• BMB Reports
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• 제42권10호
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• pp.655-660
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• 2009

The potential anti-metastasis and anti-invasion activities of early growth response gene-1 (Egr-1) and claudin-3, a tight junction (TJ)-related protein, were evaluated using histone deacetylase (HDAC) inhibitors in human hepatocarcinoma cells. The results of wound healing and Transwell assays showed that HDAC inhibitors such as trichostatin A and sodium butyrate inhibited cell migration and invasion. HDAC inhibitors markedly induced Egr-1 expression during the early period, after which expression levels decreased. In addition, the down-regulation of snail and type 1 insulin-like growth factor receptor (IGF-1R) in HDAC inhibitor- treated cells induced the upregulation of thrombospondin-1 (TSP-1), E-cadherin and claudin-3. Cells transfected with Egr-1 and claudin-3 siRNA displayed significant blockage of HDAC inhibitor-induced anti-invasive activity. Collectively, these findings indicate that the up-regulation of Egr-1 and claudin-3 are crucial steps in HDAC inhibitor-induced anti-metastasis and anti-invasion.

• BMB Reports
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• 제53권6호
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• pp.323-328
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• 2020

Matrix metalloproteinase 1 (MMP-1), a calcium-dependent zinccontaining collagenase, is involved in the initial degradation of native fibrillar collagen. Tissue necrosis factor-alpha (TNFα) is a pro-inflammatory cytokine that is rapidly produced by dermal fibroblasts, monocytes/macrophages, and keratinocytes and regulates inflammation and damaged-tissue remodeling. MMP-1 is induced by TNFα and plays a critical role in tissue remodeling and skin aging processes. However, the regulation of the MMP1 gene by TNFα is not fully understood. We aimed to find additional cis-acting elements involved in the regulation of TNFα-induced MMP1 gene transcription in addition to the nuclear factor-kappa B (NF-κB) and activator protein 1 (AP1) sites. Assessments of the 5'-regulatory region of the MMP1 gene, using a series of deletion constructs, revealed the requirement of the early growth response protein 1 (EGR-1)-binding sequence (EBS) in the proximal region for proper transcription by TNFα. Ectopic expression of EGR-1, a zinc-finger transcription factor that binds to G-C rich sequences, stimulated MMP1 promoter activity. The silencing of EGR-1 by RNA interference reduced TNFα-induced MMP-1 expression. EGR-1 directly binds to the proximal region and transactivates the MMP1 gene promoter. Mutation of the EBS within the MMP1 promoter abolished EGR-1-mediated MMP-1 promoter activation. These data suggest that EGR-1 is required for TNFα-induced MMP1 transcriptional activation. In addition, we found that all three MAPKs, ERK1/2, JNK, and p38 kinase, mediate TNFα-induced MMP-1 expression via EGR-1 upregulation. These results suggest that EGR-1 may represent a good target for the development of pharmaceutical agents to reduce inflammation-induced MMP-1 expression.

• BMB Reports
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• 제54권10호
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• pp.497-504
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• 2021

EGR1 (early growth response 1) is dysregulated in many cancers and exhibits both tumor suppressor and promoter activities, making it an appealing target for cancer therapy. Here, we used a systematic multi-omics analysis to review the expression of EGR1 and its role in regulating clinical outcomes in breast cancer (BC). EGR1 expression, its promoter methylation, and protein expression pattern were assessed using various publicly available tools. COSMIC-based somatic mutations and cBioPortal-based copy number alterations were analyzed, and the prognostic roles of EGR1 in BC were determined using Prognoscan and Kaplan-Meier Plotter. We also used bc-GenEx-Miner to investigate the EGR1 co-expression profile. EGR1 was more often downregulated in BC tissues than in normal breast tissue, and its knockdown was positively correlated with poor survival. Low EGR1 expression levels were also associated with increased risk of ER+, PR+, and HER2- BCs. High positive correlations were observed among EGR1, DUSP1, FOS, FOSB, CYR61, and JUN mRNA expression in BC tissue. This systematic review suggested that EGR1 expression may serve as a prognostic marker for BC patients and that clinicopathological parameters influence its prognostic utility. In addition to EGR1, DUSP1, FOS, FOSB, CYR61, and JUN can jointly be considered prognostic indicators for BC.

• 생명과학회지
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• 제19권7호
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• pp.949-955
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• 2009

점막 상피는 외부 인자를 감지하는 최전선의 인식부위로서 외부스트레스 자극을 하부의 반응 신호로 전달하는 주요 세포이다. 리보솜독성 반응을 유발하는 데옥시니발레놀 (DON) 및 그 관련 곰팡이 독소는 푸자륨 곰팡이 오염에 의한 식중독성 소화기 염증성 질환과의 연관성이 알려 져 있다. 본 연구의 목적은 DON이 상피세포 감지 신호 전달 분자로서 PKR과 EGR-1이 관련 되고 이들이 상피세포에서의 염증성 사이토가인 인터루킨 8의 생성에 관련 된다는 가정 하에서 연구를 수행 하였다. PKR 발현의 세포내 작용 억제는 DON에 의해 유도되는 인터루킨 8의 생성을 감소시켰다. 또한 DON에 의한 IL-8 전사 활성화는 PKR 억제에 의하여 장관 상피세포에서 감소하였다. PKR 저해제의 처리는 EGR-1 promoter 활성, mRNA, 단백질 유도 등을 감소를 유발하였으며 MAP kinase (ERK1/2, p38, JNK)는 변화가 적거나 오히려 PKR 저해제의 전처리에 의하여 항진 되었다. 결론적으로 DON에 의해 자극된 감지신호인 EGR-1은 자체적으로 또는 PKR 신호를 경유하여 인터루킨8의 생산을 항진하는데 주요한 기능을 하였다. 이를 통하여 향후 리보솜 독성 반응과 관련된 소화기 염증유발의 주요한 기전을 제공하고 있다.