Estrogen receptor alpha(ERα) is detected in more than 70% of the cases of breast cancer. Nuclear activity of ERα, a transcriptional regulator, is linked to the development of mammary tumors, whereas the extranuclear...Estrogen receptor alpha(ERα) is detected in more than 70% of the cases of breast cancer. Nuclear activity of ERα, a transcriptional regulator, is linked to the development of mammary tumors, whereas the extranuclear activity of ERα is related to endocrine therapy resistance. ERα polyubiquitination is induced by the estradiol hormone, and also by selective estrogen receptor degraders, resulting in ERα degradation via the ubiquitin proteasome system. Moreover, polyubiquitination is related to the ERα transcription cycle, and some E3-ubiquitin ligases also function as coactivators for ERα. Several studies have demonstrated that ERα polyubiquitination is inhibited by multiple mechanisms that include posttranslational modifica-tions, intera-ctions with coregula-tors, a-nd forma-tion of specific protein complexes with ERα. These events are responsible for an increase in ERα protein levels and deregulation of its signaling in breast cancers. Thus, ERα polyubiquitination inhibition may be a key factor in the progression of breast cancer and resistance to endocrine therapy.展开更多
Twenty-five years ago,Nembrot and colleagues reported amplification of the estrogen receptor alpha gene(ESR1) in breast cancer,initiating a broad and still ongoing scientific debate on the prevalence and clinical sign...Twenty-five years ago,Nembrot and colleagues reported amplification of the estrogen receptor alpha gene(ESR1) in breast cancer,initiating a broad and still ongoing scientific debate on the prevalence and clinical significance of this genetic aberration,which affects one of the most important genes in breast cancer.Since then,a multitude of studies on this topic has been published,covering a wide range of divergent results and arguments.The reported prevalence of this alteration in breast cancer ranges from 0% to 75%,suggesting that ESR1 copy number analysis is hampered by technical and interpreter issues.To date,two major issues related to ESR1 amplification remain to be conclusively addressed:(1) The extent to which abundant amounts of messenger RNA can mimic amplification in standard fluorescence in situ hybridization assays in the analysis of strongly expressed genes like ESR1,and(2) the clinical relevance of ESR1 amplification:Such relevance is strongly disputed,with data showing predictive value for response as well as for resistance of the cancer to anti-estrogen therapies,or for subsequent development of cancers in the case of precursor lesions that display amplification of ESR1.This review provides a comprehensive summary of the various views on ESR1 amplification,and highlights explanations for the contradictions and conflicting data that could inform future ESR1 research.展开更多
Objective:To study the expression of estrogen receptor alpha(ERα) in preimplantation mice embryos.Methods:Mice zygotes were collected from superovulated Kunming mice and cultured in vitro.Embryos at different develop...Objective:To study the expression of estrogen receptor alpha(ERα) in preimplantation mice embryos.Methods:Mice zygotes were collected from superovulated Kunming mice and cultured in vitro.Embryos at different developmental stages were collected at 0,24,36,48,72 and 96hours after cultivation.The expression of ERα in early mice embryos was detected by reverse transcription-PCR(RT-PCR) and immunocytochemistry.Results:The expression of ERα mRNA was detected in all of the examined embryonic stages.The relative amount of ERα mRNA showed no significant difference between 1-cell stage embryos and 4-cell stage embryos(P>0.05).However,the relative level of ERα mRNA significantly decreased(P<0.05) at 2-cell stage and was the lowest at this stage.Over 2-cell stage,the ERα mRNA relative level would increase and achieve the peak level at blastocyst stage.The location of immunocytochemistry showed that ERα immunopositive cells could be firstly detected at 8-cell stage,after which they are consistently detected until blastocyst stage.In addition,the intensity of ERα positive staining was higher at blastocyst stage compared with that at 8-cell stage and morula stage.Conclusion:ERα is expressed in preimplantation mice embryos in a temporal and spatial pattern and may be involved in regulating the development of early mice embryos,which probably plays crucial roles in early embryonic development.展开更多
BACKGROUND:Virological clearance,delayed progression to cirrhosis or liver cancer,and increased survival are the long-term goals of antiviral therapy in chronic hepatitis B patients.Identification of host factors corr...BACKGROUND:Virological clearance,delayed progression to cirrhosis or liver cancer,and increased survival are the long-term goals of antiviral therapy in chronic hepatitis B patients.Identification of host factors correlated with therapeutic response may contribute greatly to individual treatment.This study aimed at investigating whether T29C genotype polymorphism of estrogen receptor alpha(ESR1) is associated with the initial response to interferon-alpha(IFN-α)therapy in chronic hepatitis B patients.METHODS:The initial responses of 100 patients to IFN-α therapy were evaluated and compared by classifying them into three groups according to T29C genotype polymorphism of ESR1:T/T,T/C,and C/C genotype groups.Polymerase chain reaction-restriction fragment length polymorphism was used to analyze the genotype polymorphism in T29C.RESULTS:The frequency of initially combined response was markedly higher in both the T/T and T/C groups than in the C/C group(Z=10.326,P=0.006 and Z=26.247,P=0.000, respectively).In addition,the initial virological response was higher in the T/T and T/C groups than the C/C group(χ2=5.674, P=0.017 andχ2=4.980,P=0.026,respectively).In 78 initially HBeAg-positive patients,however,the frequency of initial e-antigen disappearance or seroconversion among the T/T,T/C, and C/C genotype groups was 34.15%,27.78%and 15.79%, respectively,which were not significantly different.CONCLUSION:The T29C genotype polymorphism of ESR1 is associated with the initial response to IFN-αin patients with chronic hepatitis B,and might be a significant marker for predicting the initial response to IFN-α,at least in this study population.展开更多
BACKGROUND: Studies have shown that estrogen receptor alpha (ERα), nerve growth factor(NGF), interleukin-2 (IL-2), and androgen receptor (AR) expression in the cerebellum decreaseswhen estrogen levels decrease in viv...BACKGROUND: Studies have shown that estrogen receptor alpha (ERα), nerve growth factor(NGF), interleukin-2 (IL-2), and androgen receptor (AR) expression in the cerebellum decreaseswhen estrogen levels decrease in vivo. Soybean isoflavone, a type of non-steroid estrogen withsimilar molecular structure and function to estradiol, exhibits estrogen-like characteristics.OBJECTIVE: To investigate the effects of various doses of soybean isoflavone on expression ofERα, NGF, IL-2, and AR in the cerebellum of ovariectomized rat, and to determine whether there is adose-dependent effect.DESIGN, TIME AND SETTING: Controlled trial at the cellular and molecular level. The study wasperformed at the Experimental Animal Engineering Center, College of Veterinary Medicine, SichuanAgricultural University from July 2006 to May 2008.MATERIALS: Soybean isoflavone, comprised of daidzin, genistein and isoflavone, was provided byTaiyuan Yuantai Biochemical Industry, China. The ERα, NGF, IL-2, and AR in situ hybridization kit,rabbit anti-rat ERα, NGF, IL-2, and AR monoclonal antibodies, and SABC kit were purchased fromWuhan Boster Biological Technology, China.METHODS: A total of 50 female, Sprague Dawley rats, aged 3 months, were randomly assigned to5 groups, with 10 animals in each group. With the exception of the sham-operation group (abdominalcavity opening alone), all rats underwent bilateral ovariectomy. At 14 days after surgery, rats in thehigh-, middle-, and low-dose soybean isoflavone groups were subcutaneously injected with 1.5, 1.0,and 0.5 mg/kg soybean isoflavone, respectively, every 2 days for 6 consecutive weeks. Rats in thesham-operation and ovariectomized groups were subcutaneously injected with absolute alcohol(0.5 mL/kg).MAIN OUTCOME MEASURES: Expression levels and distribution of ERα, NGF, IL-2, and AR in thecerebellum were detected by immunohistochemistry and in situ hybridization.RESULTS: Compared with the sham-operation group, immunoreactive products and hybridizationsignals of ERα, NGF, IL-2, and AR were significantly decreased in the cerebellar cortex and nuclei ofovariectomized rats (P< 0.05 or P< 0.01), but increased following soybean isoflavone treatment. Inparticular, levels of the high-dose soybean isoflavone group were almost restored to levels of thesham-operation group (P > 0.05). The immunoreactive products were primarily located in thecytoplasm and neurites, and rarely in the cell membrane and nuclei. However, the hybridizationsignals were predominantly located in the nuclei, but rarely in the cytoplasm, cell membrane, orneurites.CONCLUSION: Soybean isofiavone upregulated ERα, NGF, IL-2, and AR protein and geneexpression in a dose-dependent manner, and played an important role in sustaining and protectingstructure and function of cerebellar neurons. Moreover, the similarity of expression patterns of thesemolecules indicated that they were mutually interactive during the regulation of soybean isoflavoneto the cerebellum.展开更多
The nuclear transcription factors κB (NF-κB) is widely existing in various kinds of cell types in the nervous system and plays an important role in neuron apoptosis and neurodegenerative diseases. Estrogen receptor ...The nuclear transcription factors κB (NF-κB) is widely existing in various kinds of cell types in the nervous system and plays an important role in neuron apoptosis and neurodegenerative diseases. Estrogen receptor alpha 36 (ER-α36), is a novel variant of ERα (as known ER-α66) which can transduce both estrogenand antiestrogen-dependent activation of MAPK signal pathway and stimulate cell growth. Here, we aimed to detect the effect of ER-α36 gene silencing on the expression of NF-κB in normal cultured PC12 cells and to provide an experimental foundation for understanding the function of ER-α36 innerve cells. PC12 cells with ER-α36 expression knocked down by the shRNA method. Then Western blot and immunocytochemical staining were performed to detect the expression and translocation of NF-κB after transfection. The results showed that NF-κB expression was significantly higher comparing with the control group after transfection (P 0.01). Also, NF-κB subunit entered nuclear after transfection;Immunofluorescence staining and immunocytochemical staining of PC12 cells demonstrated that ER-α36 was expressed mainly on the plasma membrane and on the cell nucleus membrane. These data indicate that ER-α36 gene silencing can increase the expression of NF-κB and promote its nuclear translocation in PC12 cells.展开更多
Background Estrogen might play an important role in type 2 diabetes mellitus pathogenesis. A number of polymorphisms have been reported in the estrogen receptor alpha (ERα) gene (also named ESR1), including the XbaI ...Background Estrogen might play an important role in type 2 diabetes mellitus pathogenesis. A number of polymorphisms have been reported in the estrogen receptor alpha (ERα) gene (also named ESR1), including the XbaI and PvuII restriction enzyme polymorphisms of ESR1, which may be involved in disease pathogenesis. The aim of this study was to determine whether ERα gene polymorphisms are associated with type 2 diabetes mellitus and serum lipid level. Methods Two hundred and ninety-nine patients with type 2 diabetes mellitus were compared with three hundred and forty-one health controls of Guangzhou in China, both were male and postmenopausal female residents at 51-70 years. ESR1 genotyping was performed using polymerase chain reaction (PCR) and PvuII and XbaI restriction fragment length polymorphism (PCR-RFLP) analysis. Results ESR1 allelic frequencies of P, p and X, x alleles were 0.408, 0.592; 0.360, 0.640 in the type 2 diabetes mellitus group and 0.318, 0.682; 0.328, 0.672 in the control group, respectively. In case-control study, there was significant difference in PvuII, but not XbaI, allele frequency between the type 2 diabetes mellitus and control groups (P=0.001 and P=0.122). When the group was separated into men and women, the difference was significant in women (P<0.001) but not in men (P=0.854) with the PvuII genotype, and the effect of PvuII variant on the development of type 2 diabetes mellitus was improved with aging. In addition, PvuII genotype was associated with blood glucose [fasting blood glucose (FBG), postprandial blood glucose (PBG)] and serum lipid [total cholesterol (TC) and low density lipoprotein (LDL)-c] concentration in healthy women. Conclusions PvuII polymorphism of ESR1 increases susceptibility to type 2 diabetes mellitus in Chinese Guangzhou women. ESR1 variants may also impact serum lipid metabolism, which might provide a mechanism connecting ESR1 to type 2 diabetes.展开更多
Estrogen-related receptor alpha(ERRα) plays an important role in the development of hormone-dependent cancers, but its roles in lung cancer remain elusive. The present study was aimed to investigate the effects of ER...Estrogen-related receptor alpha(ERRα) plays an important role in the development of hormone-dependent 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 m RNA and protein levels of ERRα were detected in lung cancer A549 and MCF-7 cells and bronchial epithelial BEAS-2B cells by q RT-PCR and Western blotting, respectively. ERRα plasmid transfection and XCT-790(an inverse agonist of ERRα) 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 fibronectin(FN) and vimentin(Vim) and the transcription factors(Snail, Zeb1 Twist and Slug) were further detected at mR NA and protein levels by q RT-PCR and Western blotting, respectively. The results showed that ERRα promoted the growth of lung cancer A549 cells in vitro. XCT-790 significantly inhibited the migration and invasion of A549 cells. Over-expression of ERRα promoted the epithelial-to-mesenchymal transition(EMT) of A549 cells, 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 transcription factors, significantly abolished the ERRα-induced EMT of A549 cells. It was suggested that ERRα promoted the migration and invasion of A549 cells by inducing EMT, and Slug was involved in the process. Targeting ERRα might be an efficient approach for lung cancer treatment.展开更多
In the present study expression of estrogen receptor subtype -α(ERα) and -β (ERβ) in the cerebral cortex, cerebellum, and olfactory bulb was investigated and compared between neonatal (1～3-days-old) and adult (25...In the present study expression of estrogen receptor subtype -α(ERα) and -β (ERβ) in the cerebral cortex, cerebellum, and olfactory bulb was investigated and compared between neonatal (1～3-days-old) and adult (250～350g) rats, using reverse transcription-polymerase chain reaction (RT- PCR). No ERα transcripts were detectable in the adult cerebellum and olfactory bulb, whereas very weak expression of ERα was present in the adult cerebral cortex. No significant difference in ERβ transcripts was detectable between the neonatal and adult rats. While transcripts for both ER subtypes were co-expressed in these brain areas of neonatal rats, although ERα expression was significantly weaker than ERβ. Even in the cerebral cortex known to contain both ER subtypes in adult rats, ERα transcripts in neonatal rats were much higher than in adult. These observations provide evidence for the existence of different expression patterns of ERcα/ERβ transcripts in these three brain areas between the neonatal and adult rats, suggesting that each ER subtype may play a distinct role in the regulation of differentiation, development, and functions of the brain by estrogen.展开更多
Relatively little is known about the effects of estrogen on postischemic cerebral vasomotor dynamics after ischemic injury. Emerging hypotheses suggest that the timing after menopause at which hormone replacement is i...Relatively little is known about the effects of estrogen on postischemic cerebral vasomotor dynamics after ischemic injury. Emerging hypotheses suggest that the timing after menopause at which hormone replacement is initiated might be important and might modulate the potential benefits of estrogen on brain rescue once a cerebral ischemic event occurs. Therefore, we sought to determine if protracted hypoestrogenicity modifies estrogen’s protective effects on postischemic pial artery dilatory dysfunction and if the arachidonic acid metabolite 20-hydroxyeicosatetraeonic (20-HETE) contributes to the dysfunction. Pial artery dilation to acetylcholine was examined before and 1 hour after 15 minutes forebrain ischemia. The rat study groups included: sexually mature males (M), naive (N), OVX (OV), estrogen-treated OVX females (E1;estrogen started 1 week post ovariectomy) and delayed estrogen-treated (E10;started 10 weeks post ovariectomy) females. Postischemic responses were assessed before and after superfusion of the 20-HETE synthesis inhibitor N-hydroxy-N’-(4-butyl-2-methylphenyl)-formamidine (HET0016). Postischemic acetylcholine dilation was depressed in M, OV and E10 compared to N and E1 rats. Compared to E1, delayed estrogen replacement worsened acetylcholine-induced dilation. Postischemic microvascular estrogen receptor alpha (ERα) density was similar in the OV, E1 and E10 rats. Postischemic application of HET0016 failed to improve acetylcholine dilation. Continuous infusion of HET0016 during and after ischemia did not reverse postischemic pial vasodilatory dysfunction. Timing of estrogen replacement may be critical for vascular health after cerebral ischemic injury. Postischemic loss of acetylcholine reactivity does not appear to involve mechanisms related to 20-HETE synthesis or microvascular ERα expression.展开更多
基金Supported by the DGAPA-UNAM,Nos.PAPIIT–IA200916 and PAPIIT–IA201618
文摘Estrogen receptor alpha(ERα) is detected in more than 70% of the cases of breast cancer. Nuclear activity of ERα, a transcriptional regulator, is linked to the development of mammary tumors, whereas the extranuclear activity of ERα is related to endocrine therapy resistance. ERα polyubiquitination is induced by the estradiol hormone, and also by selective estrogen receptor degraders, resulting in ERα degradation via the ubiquitin proteasome system. Moreover, polyubiquitination is related to the ERα transcription cycle, and some E3-ubiquitin ligases also function as coactivators for ERα. Several studies have demonstrated that ERα polyubiquitination is inhibited by multiple mechanisms that include posttranslational modifica-tions, intera-ctions with coregula-tors, a-nd forma-tion of specific protein complexes with ERα. These events are responsible for an increase in ERα protein levels and deregulation of its signaling in breast cancers. Thus, ERα polyubiquitination inhibition may be a key factor in the progression of breast cancer and resistance to endocrine therapy.
文摘Twenty-five years ago,Nembrot and colleagues reported amplification of the estrogen receptor alpha gene(ESR1) in breast cancer,initiating a broad and still ongoing scientific debate on the prevalence and clinical significance of this genetic aberration,which affects one of the most important genes in breast cancer.Since then,a multitude of studies on this topic has been published,covering a wide range of divergent results and arguments.The reported prevalence of this alteration in breast cancer ranges from 0% to 75%,suggesting that ESR1 copy number analysis is hampered by technical and interpreter issues.To date,two major issues related to ESR1 amplification remain to be conclusively addressed:(1) The extent to which abundant amounts of messenger RNA can mimic amplification in standard fluorescence in situ hybridization assays in the analysis of strongly expressed genes like ESR1,and(2) the clinical relevance of ESR1 amplification:Such relevance is strongly disputed,with data showing predictive value for response as well as for resistance of the cancer to anti-estrogen therapies,or for subsequent development of cancers in the case of precursor lesions that display amplification of ESR1.This review provides a comprehensive summary of the various views on ESR1 amplification,and highlights explanations for the contradictions and conflicting data that could inform future ESR1 research.
文摘Objective:To study the expression of estrogen receptor alpha(ERα) in preimplantation mice embryos.Methods:Mice zygotes were collected from superovulated Kunming mice and cultured in vitro.Embryos at different developmental stages were collected at 0,24,36,48,72 and 96hours after cultivation.The expression of ERα in early mice embryos was detected by reverse transcription-PCR(RT-PCR) and immunocytochemistry.Results:The expression of ERα mRNA was detected in all of the examined embryonic stages.The relative amount of ERα mRNA showed no significant difference between 1-cell stage embryos and 4-cell stage embryos(P>0.05).However,the relative level of ERα mRNA significantly decreased(P<0.05) at 2-cell stage and was the lowest at this stage.Over 2-cell stage,the ERα mRNA relative level would increase and achieve the peak level at blastocyst stage.The location of immunocytochemistry showed that ERα immunopositive cells could be firstly detected at 8-cell stage,after which they are consistently detected until blastocyst stage.In addition,the intensity of ERα positive staining was higher at blastocyst stage compared with that at 8-cell stage and morula stage.Conclusion:ERα is expressed in preimplantation mice embryos in a temporal and spatial pattern and may be involved in regulating the development of early mice embryos,which probably plays crucial roles in early embryonic development.
基金supported by grants from the National Natural Science Foundation of China(No.30771907)the Foundation of Pre-973 Program Projects(No.2009CB526411)
文摘BACKGROUND:Virological clearance,delayed progression to cirrhosis or liver cancer,and increased survival are the long-term goals of antiviral therapy in chronic hepatitis B patients.Identification of host factors correlated with therapeutic response may contribute greatly to individual treatment.This study aimed at investigating whether T29C genotype polymorphism of estrogen receptor alpha(ESR1) is associated with the initial response to interferon-alpha(IFN-α)therapy in chronic hepatitis B patients.METHODS:The initial responses of 100 patients to IFN-α therapy were evaluated and compared by classifying them into three groups according to T29C genotype polymorphism of ESR1:T/T,T/C,and C/C genotype groups.Polymerase chain reaction-restriction fragment length polymorphism was used to analyze the genotype polymorphism in T29C.RESULTS:The frequency of initially combined response was markedly higher in both the T/T and T/C groups than in the C/C group(Z=10.326,P=0.006 and Z=26.247,P=0.000, respectively).In addition,the initial virological response was higher in the T/T and T/C groups than the C/C group(χ2=5.674, P=0.017 andχ2=4.980,P=0.026,respectively).In 78 initially HBeAg-positive patients,however,the frequency of initial e-antigen disappearance or seroconversion among the T/T,T/C, and C/C genotype groups was 34.15%,27.78%and 15.79%, respectively,which were not significantly different.CONCLUSION:The T29C genotype polymorphism of ESR1 is associated with the initial response to IFN-αin patients with chronic hepatitis B,and might be a significant marker for predicting the initial response to IFN-α,at least in this study population.
基金the Program for Changing Scholars and Innovative Research Team in University, No. IRT0848Youth Foundation of Sichuan Province Science & Technology Bureau, No. 08ZQ026-061
文摘BACKGROUND: Studies have shown that estrogen receptor alpha (ERα), nerve growth factor(NGF), interleukin-2 (IL-2), and androgen receptor (AR) expression in the cerebellum decreaseswhen estrogen levels decrease in vivo. Soybean isoflavone, a type of non-steroid estrogen withsimilar molecular structure and function to estradiol, exhibits estrogen-like characteristics.OBJECTIVE: To investigate the effects of various doses of soybean isoflavone on expression ofERα, NGF, IL-2, and AR in the cerebellum of ovariectomized rat, and to determine whether there is adose-dependent effect.DESIGN, TIME AND SETTING: Controlled trial at the cellular and molecular level. The study wasperformed at the Experimental Animal Engineering Center, College of Veterinary Medicine, SichuanAgricultural University from July 2006 to May 2008.MATERIALS: Soybean isoflavone, comprised of daidzin, genistein and isoflavone, was provided byTaiyuan Yuantai Biochemical Industry, China. The ERα, NGF, IL-2, and AR in situ hybridization kit,rabbit anti-rat ERα, NGF, IL-2, and AR monoclonal antibodies, and SABC kit were purchased fromWuhan Boster Biological Technology, China.METHODS: A total of 50 female, Sprague Dawley rats, aged 3 months, were randomly assigned to5 groups, with 10 animals in each group. With the exception of the sham-operation group (abdominalcavity opening alone), all rats underwent bilateral ovariectomy. At 14 days after surgery, rats in thehigh-, middle-, and low-dose soybean isoflavone groups were subcutaneously injected with 1.5, 1.0,and 0.5 mg/kg soybean isoflavone, respectively, every 2 days for 6 consecutive weeks. Rats in thesham-operation and ovariectomized groups were subcutaneously injected with absolute alcohol(0.5 mL/kg).MAIN OUTCOME MEASURES: Expression levels and distribution of ERα, NGF, IL-2, and AR in thecerebellum were detected by immunohistochemistry and in situ hybridization.RESULTS: Compared with the sham-operation group, immunoreactive products and hybridizationsignals of ERα, NGF, IL-2, and AR were significantly decreased in the cerebellar cortex and nuclei ofovariectomized rats (P< 0.05 or P< 0.01), but increased following soybean isoflavone treatment. Inparticular, levels of the high-dose soybean isoflavone group were almost restored to levels of thesham-operation group (P > 0.05). The immunoreactive products were primarily located in thecytoplasm and neurites, and rarely in the cell membrane and nuclei. However, the hybridizationsignals were predominantly located in the nuclei, but rarely in the cytoplasm, cell membrane, orneurites.CONCLUSION: Soybean isofiavone upregulated ERα, NGF, IL-2, and AR protein and geneexpression in a dose-dependent manner, and played an important role in sustaining and protectingstructure and function of cerebellar neurons. Moreover, the similarity of expression patterns of thesemolecules indicated that they were mutually interactive during the regulation of soybean isoflavoneto the cerebellum.
文摘The nuclear transcription factors κB (NF-κB) is widely existing in various kinds of cell types in the nervous system and plays an important role in neuron apoptosis and neurodegenerative diseases. Estrogen receptor alpha 36 (ER-α36), is a novel variant of ERα (as known ER-α66) which can transduce both estrogenand antiestrogen-dependent activation of MAPK signal pathway and stimulate cell growth. Here, we aimed to detect the effect of ER-α36 gene silencing on the expression of NF-κB in normal cultured PC12 cells and to provide an experimental foundation for understanding the function of ER-α36 innerve cells. PC12 cells with ER-α36 expression knocked down by the shRNA method. Then Western blot and immunocytochemical staining were performed to detect the expression and translocation of NF-κB after transfection. The results showed that NF-κB expression was significantly higher comparing with the control group after transfection (P 0.01). Also, NF-κB subunit entered nuclear after transfection;Immunofluorescence staining and immunocytochemical staining of PC12 cells demonstrated that ER-α36 was expressed mainly on the plasma membrane and on the cell nucleus membrane. These data indicate that ER-α36 gene silencing can increase the expression of NF-κB and promote its nuclear translocation in PC12 cells.
文摘Background Estrogen might play an important role in type 2 diabetes mellitus pathogenesis. A number of polymorphisms have been reported in the estrogen receptor alpha (ERα) gene (also named ESR1), including the XbaI and PvuII restriction enzyme polymorphisms of ESR1, which may be involved in disease pathogenesis. The aim of this study was to determine whether ERα gene polymorphisms are associated with type 2 diabetes mellitus and serum lipid level. Methods Two hundred and ninety-nine patients with type 2 diabetes mellitus were compared with three hundred and forty-one health controls of Guangzhou in China, both were male and postmenopausal female residents at 51-70 years. ESR1 genotyping was performed using polymerase chain reaction (PCR) and PvuII and XbaI restriction fragment length polymorphism (PCR-RFLP) analysis. Results ESR1 allelic frequencies of P, p and X, x alleles were 0.408, 0.592; 0.360, 0.640 in the type 2 diabetes mellitus group and 0.318, 0.682; 0.328, 0.672 in the control group, respectively. In case-control study, there was significant difference in PvuII, but not XbaI, allele frequency between the type 2 diabetes mellitus and control groups (P=0.001 and P=0.122). When the group was separated into men and women, the difference was significant in women (P<0.001) but not in men (P=0.854) with the PvuII genotype, and the effect of PvuII variant on the development of type 2 diabetes mellitus was improved with aging. In addition, PvuII genotype was associated with blood glucose [fasting blood glucose (FBG), postprandial blood glucose (PBG)] and serum lipid [total cholesterol (TC) and low density lipoprotein (LDL)-c] concentration in healthy women. Conclusions PvuII polymorphism of ESR1 increases susceptibility to type 2 diabetes mellitus in Chinese Guangzhou women. ESR1 variants may also impact serum lipid metabolism, which might provide a mechanism connecting ESR1 to type 2 diabetes.
基金supported by the Fundamental Research Funds of the Central Universities(No.21613316)
文摘Estrogen-related receptor alpha(ERRα) plays an important role in the development of hormone-dependent 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 m RNA and protein levels of ERRα were detected in lung cancer A549 and MCF-7 cells and bronchial epithelial BEAS-2B cells by q RT-PCR and Western blotting, respectively. ERRα plasmid transfection and XCT-790(an inverse agonist of ERRα) 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 fibronectin(FN) and vimentin(Vim) and the transcription factors(Snail, Zeb1 Twist and Slug) were further detected at mR NA and protein levels by q RT-PCR and Western blotting, respectively. The results showed that ERRα promoted the growth of lung cancer A549 cells in vitro. XCT-790 significantly inhibited the migration and invasion of A549 cells. Over-expression of ERRα promoted the epithelial-to-mesenchymal transition(EMT) of A549 cells, 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 transcription factors, significantly abolished the ERRα-induced EMT of A549 cells. It was suggested that ERRα promoted the migration and invasion of A549 cells by inducing EMT, and Slug was involved in the process. Targeting ERRα might be an efficient approach for lung cancer treatment.
文摘In the present study expression of estrogen receptor subtype -α(ERα) and -β (ERβ) in the cerebral cortex, cerebellum, and olfactory bulb was investigated and compared between neonatal (1～3-days-old) and adult (250～350g) rats, using reverse transcription-polymerase chain reaction (RT- PCR). No ERα transcripts were detectable in the adult cerebellum and olfactory bulb, whereas very weak expression of ERα was present in the adult cerebral cortex. No significant difference in ERβ transcripts was detectable between the neonatal and adult rats. While transcripts for both ER subtypes were co-expressed in these brain areas of neonatal rats, although ERα expression was significantly weaker than ERβ. Even in the cerebral cortex known to contain both ER subtypes in adult rats, ERα transcripts in neonatal rats were much higher than in adult. These observations provide evidence for the existence of different expression patterns of ERcα/ERβ transcripts in these three brain areas between the neonatal and adult rats, suggesting that each ER subtype may play a distinct role in the regulation of differentiation, development, and functions of the brain by estrogen.
文摘Relatively little is known about the effects of estrogen on postischemic cerebral vasomotor dynamics after ischemic injury. Emerging hypotheses suggest that the timing after menopause at which hormone replacement is initiated might be important and might modulate the potential benefits of estrogen on brain rescue once a cerebral ischemic event occurs. Therefore, we sought to determine if protracted hypoestrogenicity modifies estrogen’s protective effects on postischemic pial artery dilatory dysfunction and if the arachidonic acid metabolite 20-hydroxyeicosatetraeonic (20-HETE) contributes to the dysfunction. Pial artery dilation to acetylcholine was examined before and 1 hour after 15 minutes forebrain ischemia. The rat study groups included: sexually mature males (M), naive (N), OVX (OV), estrogen-treated OVX females (E1;estrogen started 1 week post ovariectomy) and delayed estrogen-treated (E10;started 10 weeks post ovariectomy) females. Postischemic responses were assessed before and after superfusion of the 20-HETE synthesis inhibitor N-hydroxy-N’-(4-butyl-2-methylphenyl)-formamidine (HET0016). Postischemic acetylcholine dilation was depressed in M, OV and E10 compared to N and E1 rats. Compared to E1, delayed estrogen replacement worsened acetylcholine-induced dilation. Postischemic microvascular estrogen receptor alpha (ERα) density was similar in the OV, E1 and E10 rats. Postischemic application of HET0016 failed to improve acetylcholine dilation. Continuous infusion of HET0016 during and after ischemia did not reverse postischemic pial vasodilatory dysfunction. Timing of estrogen replacement may be critical for vascular health after cerebral ischemic injury. Postischemic loss of acetylcholine reactivity does not appear to involve mechanisms related to 20-HETE synthesis or microvascular ERα expression.
