Effects of Estrogen-related Receptor alpha (ERRα) on Proliferation and Metastasis of Human Lung Cancer A549 Cells

Estrogen-related receptor alpha （ERRα） plays an important role in the development of hor- monezdependent cancers, but its roles in lung cancer remain elusive. The present study was aimed to investigate the effects of ERRα on the proliferation and metastasis of lung cancer A549 cells. The mRNA and protein levels of ERRor were detected in lung cancer A549 and MCF-7 cells and bronchial epithelial BEAS-2B cells by qRT-PCR and Western blotting, respectively. ERRor plasmid transfection and XCT-790 （an inverse agonist of ERRc0 were used to up-regulate or down-regulate ERRα expression in A549 cells, respectively. The viability of A549 cells was measured by cell counting kit-8 （CCK-8） and the motility of A549 cells by wound healing assay and Transwell migration/invasion assay. The epithelial markers E-cadherin （E-Cad） and zona occludin-1 （ZO-1）, the mesenchymal markers fi- bronectin （FN） and vimentin （Vim） and the transcription factors （Snail, Zebl Twist and Slug） were fur- ther detected at mRNA and protein levels by qRT-PCR and Western blotting, respectively. The results showed that ERRor promoted the growth of lung cancer A549 cells in vitro. XCT-790 significantly in- hibited the migration and invasion of A549 cells. Over-expression of ERRα promoted the epithe- lial-to-mesenchymal transition （EMT） of A549 ceils, down-regulated the epithelial makers E-Cad and ZO-1, and up-regulated the mesenchymal makers FN and Vim. Silencing of Slug, but not other tran- scription factors, significantly abolished the ERRs-induced EMT of A549 cells. It was suggested that ERRor promoted the migration and invasion of A549 cells by inducing EMT, and Slug was involved in the process. Targeting ERRor might be an efficient approach for lung cancer treatment.

A Review Study on the Effects of Estrogen Level on Vaginal Candida spp.of Women with Estrogen-Related Receptor Breast Cancer

The aim of the present study have been reported to review the estrogen level in the patients with the breast cancer and healthy individuals.Breast cancer is one of the most common diseases in women worldwide that is characterized by uncontrolled growth of malignant cells in the mammary epithelial tissue.The estrogen was found at normal level in most patients with ER-positive breast cancer and in healthy individuals,while its high level was higher among patients with ER-negative breast cancer.Many studies show evidences about the role of estrogen at a high level on the development of breast cancer.The association between the estrogen levels and the presence of Candida spp.in vagina of patients with breast cancer was reviewed.

Pan-retinal ganglion cell markers in mice, rats, and rhesus macaques

Univocal identification of retinal ganglion cells(RGCs) is an essential prerequisite for studying their degeneration and neuroprotection. Before the advent of phenotypic markers, RGCs were normally identified using retrograde tracing of retinorecipient areas. This is an invasive technique, and its use is precluded in higher mammals such as monkeys. In the past decade, several RGC markers have been described. Here, we reviewed and analyzed the specificity of nine markers used to identify all or most RGCs, i.e., pan-RGC markers, in rats, mice, and macaques. The best markers in the three species in terms of specificity, proportion of RGCs labeled, and indicators of viability were BRN3A, expressed by vision-forming RGCs, and RBPMS, expressed by vision-and non-vision-forming RGCs. NEUN, often used to identify RGCs, was expressed by non-RGCs in the ganglion cell layer, and therefore was not RGC-specific. γ-SYN, TUJ1, and NF-L labeled the RGC axons, which impaired the detection of their somas in the central retina but would be good for studying RGC morphology. In rats, TUJ1 and NF-L were also expressed by non-RGCs. BM88, ERRβ,and PGP9.5 are rarely used as markers, but they identified most RGCs in the rats and macaques and ERRβ in mice. However, PGP9.5 was also expressed by non-RGCs in rats and macaques and BM88 and ERRβ were not suitable markers of viability.

Estrogen-related receptor γ disruption of source water and drinking water treatment processes extracts

Environmental chemicals in drinking water can impact human health through nuclear receptors. Additionally, estrogen-related receptors （ERRs） are vulnerable to endocrine-disrupting effects. To date, however, ERR disruption of drinking water potency has not been reported. We used ERRy two-hybrid yeast assay to screen ERRy disrupting activities in a drinking water treatment plant （DWTP） located in north China and in source water from a reservoir, focusing on agonistic, antagonistic, and inverse agonistie activity to 4-hydroxytamoxifen （4-OHT）. Water treatment processes in the DWTP consisted of pre-chlorination, coagulation, coal and sand filtration, activated carbon filtration, and secondary chlorination processes. Samples were extracted by solid phase extraction. Results showed that ERRγ antagonistic activities were found in all sample extracts, but agonistic and inverse agonistic activity to 4-OHT was not found. When calibrated with the toxic equivalent of 4-OHT, antagonistic effluent effects ranged from 3.4 to 33.1 μg/L. In the treatment processes, secondary chlorination was effective in removing ERRy antagonists, but the coagulation process led to significantly increased ERRy antagonistic activity. The drinking water treatment processes removed 73.5 % of ERRy antagonists. To our knowledge, the occurrence of ERRy disruption activities on source and drinking water in vitro had not been reported previously. It is vital, therefore, to increase our understanding of ERRγ disrupting activities in drinking water.

Emerging role of the orphan nuclear receptor estrogen-related receptor gamma in liver metabolic diseases

Estrogen-related receptor gamma(ERRg)is one of three members of the ERR family and remains an orphan,as there are no known natural ligands.ERRg is an inducible transcription factor,and its ligandindependent transcriptional activity is regulated by co-regulator interactions and post-transcriptional modifications.Recent findings from animal models show that ERRg,as a downstream mediator of multiple extracellular signals,plays a key role in coordinating endocrine and metabolic signals,resulting in changes in glucose,alcohol,lipid,and iron metabolism in the liver.Therefore,dysregulation of this receptor contributes to the pathogenesis of metabolic diseases such as hyperglycemia,insulin resistance,and alcoholic liver injury.Interestingly,ERRg is also involved in responses to bacterial infection.These findings establish the importance of ERRg in the endocrine and metabolic control of liver metabolism,and suggest that ERRg may be a promising therapeutic target for metabolic diseases of the liver.

Transcriptional regulation of VEGF expression by estrogen-related receptor γ

Vascular endothelial growth factor(VEGF)is associated with endothelial cell proliferation,migration and angiogenesis.Estrogen-related receptorγ(ERRγ)plays important regulatory roles in fatty acid oxidation,mitochondrial biogenesis and gluconeogenesis.Recently,ERRγ has been shown to be involved in angiogenesis;however,the mechanism of ERRγ-mediated angiogenesis is poorly understood.Here the results show that ERRγactivates VEGF gene transcription via two putative estrogen-related receptor binding elements(ERREs)mapped to the promoter region.Chromatin immunoprecipitation assays confirmed that ERRγ binds to the identified ERREs.Adenovirus-mediated overexpression of ERRγ increased the expression of VEGF gene and induced an increase in VEGF secretion in C2C12 myotubes.In contrast,the secretion of VEGF was significantly decreased in the presence of the ERRγ inverse agonist GSK5182.Furthermore,treatment of human umbilical vein endothelial cells(HUVECs)with the conditioned medium from ERRγ-overexpressing C2C12 myotubes significantly increased proliferation,migration and tube formation.These data indicate that VEGF functions as a downstream target gene of ERRγ and mediates the effects of ERRγ on endothelial cells proliferation,migration and angiogenesis.This physiological function of ERRγ might provide a novel target for treatment of ischemic diseases.

BPH-1通过分泌PGE2上调前列腺间质细胞ERRα的表达

雌激素受体相关受体α(estrogen receptor-related receptorα,ERRα)是一类可以直接或间接参与雌激素应答反应的孤儿核受体,它与雌激素受体(estrogen receptor,ER)在结构上有很强的同源性.雌激素效应在良性前列腺增生(benign prostatic hyperplasis,BPH)的发生和发展中起着重要的作用.通常,孤儿核受体的转录活性多受一些非经典激素如维生素A衍生物、前列腺素类、固醇的调控.本文研究前列腺上皮细胞分泌的活性因子对间质细胞ERRα表达调控的分子机制.收集前列腺增生上皮细胞系BPH-1和前列腺癌上皮细胞系DU-145的条件培养液(condition medium,CM)培养间质细胞,采用实时定量RT-PCR和Western印迹法检测前列腺间质细胞(prostatic stromal cells,PrSC)中ERRα的表达,筛选CM中影响ERRα表达的活性因子.研究结果显示,BPH-1的CM可以上调ERRα的表达,而DU-145的CM对ERRα的表达没有影响;BPH-1中合成前列腺素E2(prostaglandin E2,PGE2)的限速酶———环氧合酶2(cyclooxygenase-2,COX-2)的mRNA表达水平和PGE2的分泌水平明显高于DU-145中COX-2表达水平和PGE2分泌水平;用经添加COX-2抑制剂NS-398的培养液处理BPH-1,其CM中PGE2的浓度明显下降,并失去了对ERRα表达的上调作用;添加PGE2可上调间质细胞中ERRα的表达.结果表明,BPH-1通过分泌PGE2促进间质细胞ERRα的表达,提示:在良性前列腺增生的发生和发展中,上皮细胞的旁分泌作用可促进间质细胞由ERRα介导的雌激素效应.

Errα通过抑制β-Catenin促进猪前体脂肪细胞成脂分化(英文)

雌激素相关受体α(Errα)和Wnt/β-Catenin信号通路都能够调控成脂分化.研究表明Errα和wnt/β-Catenin信号通路之间存在互作,β-联蛋白(β-Catenin)是Wnt/β-Catenin信号通路的关键因子.为了研究Errα和β-Catenin在脂肪生成中的相互作用,在293A细胞中包装得到Errα腺病毒并侵染猪前体脂肪细胞.LiCl和XCT790被用于不同处理的猪前体脂肪细胞.蛋白质印迹实验发现,在成脂分化过程中,Errα表达升高,β-Catenin表达降低.显微观察绿色荧光发现,Errα腺病毒能够侵染猪前体脂肪细胞.蛋白质印迹实验显示,在猪前体脂肪细胞中,Errα腺病毒促进Errα表达,XCT790抑制Errα表达.油红O染色结果表明,β-Catenin抑制成脂分化,而Errα通过抑制β-Catenin促进成脂分化.进一步的蛋白质印迹实验表明,在猪前体脂肪细胞成脂分化过程中,LiCl能够稳定β-Catenin表达,Errα抑制β-Catenin表达.这些发现提示,Errα通过抑制β-Catenin表达来促进成脂分化.

Molecular Mediators of Estrogen Reduction-induced Otolith Shedding

Objective Previous study suggested that estradiol(E2)plays an important role in otolith shedding by regulating the expression of otoconin 90(OC90).The purpose of this article is to provide further data on the effect and mechanism of E2 on the morphology of otolith.Methods The rats receiving bilateral ovariectomy(OVX)were used as animal models.Co-immunoprecipitation was used to observe the relationship between estrogen receptor(ER)and estrogen-related receptorα(ERRα).The morphology of otolith was observed under the scanning electron microscopy.Western blotting and qPCR were used for quantitative analysis of the roles of ER and ERRαin regulating OC90 expression.Results The looser otoliths were observed in rats receiving bilateral OVX,which could be reversed by supplementation with E2.The level of ERRαwas decreased in bilateral OVX rats.ER and ERRαinteracted with each other on the regulation of the expression of OC90.Conclusion Our results suggest ER and ERRαare both important downstream receptors involved in regulating OC90 expression in utricles of rats,and ERRαprobably functions by interacting with ER.This provides evidence for the mechanism of otolith shedding.And it may be significant for future studies of targeted prevention and therapies for benign paroxysmal positional vertigo.