• 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.

• 동의신경정신과학회지
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• 제14권1호
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• pp.1-16
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• 2003

Objective : This study was designed to assess the protective effects of Hwangryeonhaedoktang on the animal model of depression, induced by chronic mild stress(CMS). Method : Male Sprague-Dawley rats were used for this experiment. The subjects were divided into 3 groups ( 1. CMS-drug: Hwangryeonhaedoktang administered during CMS treatment, 2. CMS-vehicle: water administered, 3. normal ). After 4 weeks of CMS treatment, they were executed forced swimming test(FST), open field test and c-Fos in paraventricular nucleus(PVN) were measured. Result : 1. In FST, immobility behavior decreased significantly in CMS-drug group. 2. There was no difference in the open field test between 3 groups 3. c-Fos expressed cell bodies in PVN were significantly less in CMS-drug than in CMS-vehicle group. Conclusion : These results suggest that Hwangryeonhaedoktang may have protective antidepressant effects in CMS model rats. And these effects could be explained by the elevated stress-copying behaviors which are related with PVN of hypothalamus.

• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.691-697
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• 1997

The mechanisms underlying opiate tolerance and dependence are not fully understood. We used human neuroblastoma SH-SY5Y cells as a model system for studying effects of morphine tolerance and withdrawal on c-myc induction and cAMP levels. It has been reported that regulation of c-fos by acute and chronic morphine withdrawal is mediated through alterations in CREB transcription factor. In this study, we examined the effects of morphine tolerance on c-myc expression and cAMP concentrations. The activation of opiate receptors by an acute morphine administration resulted in an increase in c-myc mRNA and a decrease in cAMP concentrations in a dose-dependent manner $(5,\;10,\;15,\;and\;20\;{\mu}M)$. On the other hand, the chronic treatment of morphine $(10\;{\mu}M\;for\;six\;days)$ did not induce the elevated expression of c-myc mRNA. The c-myc expression was slightly inhibited in comparison with that of the acute morphine response. However, cAMP concentrations were increased with regard to morphine withdrawal response. These results suggest that the alterations in c-myc expression might imply a significant opiate regulation relating to morphine tolerance. This observation differs from increased expression of c-fos via regulation of cAMP pathway.

• Journal of Acupuncture Research
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• 제24권2호
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• pp.211-220
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• 2007

Objectives : This study was to investigate the effect of high frequency electroacupuncture at $ST_{36}$ acupuncture point on the Complete Freund's Adjuvant (CFA) induced rat arthritis pain model. Methods : Arthritis was induced by intradermal injection of CFA into base of tail. Experimental groups were divided into 4 groups; Normal, Control and Jok-Samri ($ST_{36}$) and Non-Acupuncture point (NA). Normal group, non-arthritic group, was injected with normal saline，and the others groups were injected CFA. $ST_{36}$ group was treated by 120 Hz electroacupuncture at $ST_{36}$ acupuncture point, and NA group was treated by 120 Hz electroacupuncture at non-acupuncture point. Each groups were evaluated by the change of c-fos positive neurons in periaqueductal gray (PAG) and hippocampus by using an image analyzer and a microscope. Results: - In the PAG region, the number of fos-positive cells in the $ST_{36}$ group ($42.37{\pm}5.08$) were significantly (p<0.05) decreased compared with the control group ($64.56{\pm}6.35$). - In the PAG region, the number of fos-positive cells in the NA group were meaninglessly decreased compared with the control group - In the Cornu Ammonis(CA)l region of hippocampus, the number of fos-positive cells in the $ST_{36}$ group ($7.00{\pm}1.08$) and NA group ($5.56{\pm}2.01$) were significantly (p<0.05) decreased compared with the control group ($13.81{\pm}1.24$). - In the dentate gyrus region of hippocampus, the number of fos- positive cells in the $ST_{36}$ group ($10.75{\pm}0.98$) and NA group ($6.56{\pm}0.78$) were significantly (p$26.45{\pm}1.82$). Conclusions : It is expected that high frequency electroacupuncture can be used a treatment of arthritic pain.

• Clinical and Experimental Pediatrics
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• 제46권7호
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• pp.695-701
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• 2003

목 적 : 근육과 관절 등에서 유발된 심부통증(deep pain)이 척수상위로 전달되는 신경로에 대해서는 아직 잘 알려져 있지 않다. 그러나 최근 일부 연구자들은 피부에서 유발된 천부통증(superficial pain)과는 달리 중뇌의 PAG에 위치한 신경원에 침해 자극이 전달되어 자율신경계와 행동양식에 영향을 줄 것이라는 가설을 보고하였다. 또한, 비스테로이드성의 항염증성 약품들은 말초조직에서 프로스타글란딘 합성을 방해하여 진통효과를 유발시킨다고 알려져 왔으나 최근에는 척수와 뇌간에서도 진통효과가 있을 것이라고 추측하고 있다. 그러므로 이 연구자는 포르말린으로 체성 심부통증을 유발시켜 중뇌의 어느 부위에서 신경세포가 활성화되는지를 c-Fos 단백의 발현으로 확인하고 또한 비스테로이드성의 항염증성 약품인 아스피린의 효과를 알아보고자 이 연구를 시도하게 되었다. 방 법 : 실험 I군에서는 생리식염수를 흰쥐 꼬리에 미리 피하주사한 뒤 포르말린을 이용해 체성 심부통증을 유발시켰고, 실험 II군은 아스피린을 주사한 후 포르말린으로 체성 심부통증을 유발시켰다. 정상군에서는 통증자극을 주지 않았다. 실험 I군과 실험 II군의 흰쥐는 통증을 유발 시킨 뒤 30분, 1, 2, 6, 24시간에 희생시켜 뇌를 적출하여 뇌절편을 만들었다. 뇌절편으로 냉동 연속조직절편을 제작하여 면역조직화학적 방법으로 c-Fos 단백의 출현여부를 확인하였다. Interaural 1.00-1.36 mm를 통과하는 관상 뇌절편의 연속조직표본에서 나타난 양성면역반응성을 토대로 중뇌의 VLPAG와 DMPAG를 관찰하였고, 단위면적($0.2mm^2$)당 면역양성반응을 보인 신경세포를 계수하고 통계 처리하였다. 결 과 : c-Fos 양성면역반응 신경세포 수는 DMPAG에서 보다 VLPAG에서 현저하게 많았다. DMPAG와 VLPAG에서 통증유발 2시간 후 c-Fos 양성면역반응 신경세포 수는 최고치에 도달하였다. 아스피린을 투여한 군의 c-Fos 양성면역반응 신경세포 수는 투여하지 않은 군보다 전시기에 걸쳐 적었다. 결 론 : 이 연구결과는 포르말린에 의해 유발된 체성 심부통증의 기전과 아스피린의 효과를 이해하는데 기초적인 자료로 이용될 수 있을 것으로 생각된다.

• 약학회지
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• 제41권5호
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• pp.629-637
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• 1997

Tumor necrosis factor-${alpha}$ (TNF) induced a cytotoxic response in ME-180 cervical carcinoma cells in vitro. This cytotoxic response was accompanied by a temporal series of mitogenic stimuli : increased c-fos, c-jun and jun-B expression. Depletion of protein kinase C (PKC) by exposure of ME-180 cells to 100ng/ml phorbol myristate acetate (PMA) for 24hours almost completely abolished TNF-mediated increase in these signals, indicating that a PKC-dependent pathway is involved in TNF-mediated increases in the expression of c-fos, c-jun and jun-B. Characteristics of TNF receptors after exposure to 100ng/ml PMA or 24hours were not altered, suggesting that diminished induction of these oncogenes by TNF after PMA treatment is not due to any changes at the receptor level. To examine whether a PKC-dependent pathway is involved in TNF-mediated cytotoxicity in ME-180 cells, cytotoxicity was measured after depletion of PKC. No apparent changes in cytototoxicity after PKC depletion suggest that a PKC-dependent pathway is not involved in TNF-mediated cytotoxicity. Furthermore, results from cytotoxicity tests after exposure to staurosporine (PKC inhibitor) did not show any changes in the TNF-mediated cytotoxicity, confirming that a PKC-dependent pathway is not involved in this process. These data indicate that 1) TNF induces expression of c-fos, c-jun and jun-B oncogenes via a PKC-dependent pathway and 2) PKC-dependent expression of these three oncogenes by TNF may not be involved in TNF-mediated cytotoxicity in ME-180 cells.

• The Korean Journal of Physiology and Pharmacology
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• 제9권2호
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• pp.117-123
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• 2005

A cumulative evidence indicates that consumption of tea catechin, flavan-3-ol derived from green tea leaves, lowers the risk of cardiovascular diseases. However, a precise mechanism for this cardiovascular action has not yet been fully understood. In the present study, we investigated the effects of different green tea catechins, such as epigallocatechin-3 gallate (EGCG), epigallocatechin (EGC), epicatechin-3 gallate (ECG), and epicatechin (EC), on angiotensin II (Ang II)-induced hypertrophy in primary cultured rat aortic vascular smooth muscle cell (VSMC). [$^3H$]-leucine incorporation was used to assess VSMC hypertrophy, protein kinase assay, and western blot analysis were used to assess mitogen-activated protein kinase (MAPK) activity, and RT-PCR was used to assess c-jun or c-fos transcription. Ang II increased [$^3H$]-leucine incorporation into VSMC. However, EGCG and ECG, but not EGC or EC, inhibited [$^3H$]-leucine incorporation increased by Ang II. Ang II increased phosphorylation of c-Jun, extracellular-signal regulated kinase (ERK) 1/2 and p38 MAPK in VSMC, however, EGCG and ECG , but not EGC or EC, attenuated c-Jun phosphorylation increased by Ang II. ERK 1/2 and p38 MAPK phosphorylation induced by Ang II were not affected by any catechins. Ang II increased c-jun and c-fos mRNA expression in VSMC, however, EGCG inhibited c-jun but not c-fos mRNA expression induced by Ang II. ECG, EGC and EC did not affect c-jun or c-fos mRNA expression induced by Ang II. Our findings indicate that the galloyl group in the position 3 of the catechin structure of EGCG or ECG is essential for inhibiting VSMC hypertrophy induced by Ang II via the specific inhibition of JNK signaling pathway, which may explain the beneficial effects of green tea catechin on the pathogenesis of cardiovascular diseases observed in several epidemiological studies.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제37권3호
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• pp.195-204
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• 2011

Introduction: This study examined the regulatory mechanism underlying the meal-induced changes in the hypothalamic-pituitary-adrenal gland (HPA) axis activity. Materials and Methods: Male Sprague-Dawley rats (250-300 g) were hired for two different experiments as follows; 1) rats received either 8% sucrose or 0.2% saccharin ad libitum after 48 h of food deprivation with the gastric fistula closed (real feeding) or opened (sham feeding). 2). rats received 5 ml of intra-oral infusion with 0.2% saccharin or distilled water after 48 h of food deprivation. One hour after food access, all rats were sacrificed by a transcardiac perfusion with 4% paraformaldehyde. The brains were processed for c-Fos immunohistochemistry and the cardiac blood was collected for the plasma corticosterone assay. Results: Real feedings with sucrose or saccharin and sham feeding saccharin but not sucrose, following food deprivation decreased the plasma corticosterone level. c-Fos expression in the nucleus tractus of solitarius (NTS) of the fasted rats was increased by the consumption of sucrose but not saccharin, regardless of the feeding method. On the other hand, the consumption of sucrose or saccharin with real feeding but not the sham, induced c-Fos expression in the paraventricular nucleus (PVN) of the fasted rats. The intra-oral infusion with saccharin or water decreased the plasma corticosterone level of the fasted rats. Intra-oral water infusion increased c-Fos expression in both the PVN and NTS, but saccharin only in the NTS in the fasted rats. Conclusion: Neither restoration of the fasting-induced elevation of plasma corticosterone nor the activation of neurons in the PVN and NTS after refeeding requires the palatability of food or the post-ingestive satiety and caloric load. In addition, neuronal activation in the hypothalamic PVN may not be an implication in the restoration of the fasting-induced elevation of the plasma corticosterone by oropharyngeal stimuli of palatable food.

• Korean Journal of Acupuncture
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• 제24권4호
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• pp.99-110
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• 2007

Objectives : Epilepsy is one of the most common serious brain disorders that affect people of all ages, and it is characterized by recurrent unprovoked seizures. We examined whether acupuncture can reduce both the incidence of seizures and hippocampal cell death in dentate gyrus (DG) using a mouse model of kainic acid (KA)-induced epilepsy. Methods : ICR mice ($20{\sim}25$ g) were given acupuncture once a day at acupoint HT8 (sobu) bilaterally during 2 days before KA injection. After an intracerebroventricular injection of 0.1${\mu}g$ of KA, acupuncture treatment was subsequently administered once more (total 3 times), and the degree of seizure was observed for 20 min. Three hours after injection, we confirmed the neural cell death using cresyl violet staining and silver impregnation staining, and determined the expressions of c-Fos and glutamate decarboxylase (GAD)-67 using immunohistochemistry techniques in the DG. Results : KA induced epileptic seizure, neural cell death, increased c-Fos expression and decreased GAD-67 expression in the DG. Acupuncture treatment at HT8 reduced the severity of the epileptic seizure and inhibited neural cell death from KA. In addition, acupuncture normalized the expressions of c-Fos and GAD-67 in the same areas. Conclusions : These results demonstrated that acupuncture treatment at HT8 may reduce the KA-induced epileptic seizure and neural cell death in the DG possibly by normalizing c-Fos expressions and the gamma-aminobutyric acid neurons.

• 동의생리병리학회지
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• 제21권6호
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• pp.1483-1490
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• 2007

This study was carried out to investigate the effects of GCP treatment on the expression of NOS, c-fos, serotonin and substance P in central nerve system of monosodium iodoacetate(MIA)-induced osteoarthritic pain model. Arthritis was induced by injection of MIA(0.5 mg) into knee joint cavities of rats. Arthritic rats were divided into control(n=8) and treated(n=8) group. Control group was taken distilled water for 20 days. Treated group was taken extracts of GCP by oraly for same duration. Normal group(n=8) was infected with normal saline and was taken distilled water for 20 days. The numbers of NADPH-d positive cells in superficial dorsal horn of spinal cord of treated group($21{\pm}5$) was significantly (p<0.01) decreased compared with control($33{\pm}5$). The numbers of NADPH-d positive cell in dorsolateral periaqueductal gray matter of treated group($111{\pm}16$) was significantly(p<0.01) decreased compared with control($143{\pm}14$). The numbers of c-fos positive cells in dorsal periaqueductal gray matter of treated group($57{\pm}16$) was significantly(p<0.01) decreased compared with control($78{\pm}13$). The numbers of c-fos positive cells in paraventricular thalamic nucleus of treated group($60{\pm}15$) was significantly decreased compared with control($88{\pm}27$). The numbers of serotonin positive cells in median raphe nucleus of treated group($171{\pm}31$) was significantly(p<0.05) decreased compared with control($217{\pm}48$). On the basis of these results, we concluded that GCP treatment has inhibiting effects on the pain transmission in monosodium iodoacetate-induced osteoarthritic pain model in rat.