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 ...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.展开更多
AIM To investigate gender-specific liver estrogen receptor(ER) expression in normal subjects and patients with hepatitis C virus(HCV)-related cirrhosis and hepatocellular carcinoma(HCC).METHODS Liver tissues from norm...AIM To investigate gender-specific liver estrogen receptor(ER) expression in normal subjects and patients with hepatitis C virus(HCV)-related cirrhosis and hepatocellular carcinoma(HCC).METHODS Liver tissues from normal donors and patients diagnosed with HCV-related cirrhosis and HCV-related HCC were obtained from the NIH Liver Tissue and Cell Distribution System. The expression of ER subtypes, ERα and ERβ, were evaluated by Western blotting and real-time RT-PCR. The subcellular distribution of ERα and ERβ was further determined in nuclear and cytoplasmic tissue lysates along with the expression ofinflammatory [activated NF-κB and IκB-kinase(IKK)] and oncogenic(cyclin D1) markers by Western blotting and immunohistochemistry. The expression of ERα and ERβ was correlated with the expression of activated NF-κB, activated IKK and cyclin D1 by Spearman's correlation. RESULTS Both ER subtypes were expressed in normal livers but male livers showed significantly higher expression of ERα than females(P < 0.05). We observed significantly higher m RNA expression of ERα in HCV-related HCC liver tissues as compared to normals(P < 0.05) and ERβ in livers of HCV-related cirrhosis and HCV-related HCC subjects(P < 0.05). At the protein level, there was a significantly higher expression of nuclear ERα in livers of HCV-related HCC patients and nuclear ERβ in HCV-related cirrhosis patients as compared to normals(P < 0.05). Furthermore, we observed a significantly higher expression of phosphorylated NF-κB and cyclin D1 in diseased livers(P < 0.05). There was a positive correlation between the expression of nuclear ER subtypes and nuclear cyclin D1 and a negative correlation between cytoplasmic ER subtypes and cytoplasmic phosphorylated IKK in HCV-related HCC livers. These findings suggest that dysregulated expression of ER subtypes following chronic HCVinfection may contribute to the progression of HCVrelated cirrhosis to HCV-related HCC.CONCLUSION Gender differences were observed in ERα expression in normal livers. Alterations in ER subtype expression observed in diseased livers may influence genderrelated disparity in HCV-related pathogenesis.展开更多
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 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.
基金Supported by Cancer Sucks,Bixby,Oklahoma Research grantto Kaul R
文摘AIM To investigate gender-specific liver estrogen receptor(ER) expression in normal subjects and patients with hepatitis C virus(HCV)-related cirrhosis and hepatocellular carcinoma(HCC).METHODS Liver tissues from normal donors and patients diagnosed with HCV-related cirrhosis and HCV-related HCC were obtained from the NIH Liver Tissue and Cell Distribution System. The expression of ER subtypes, ERα and ERβ, were evaluated by Western blotting and real-time RT-PCR. The subcellular distribution of ERα and ERβ was further determined in nuclear and cytoplasmic tissue lysates along with the expression ofinflammatory [activated NF-κB and IκB-kinase(IKK)] and oncogenic(cyclin D1) markers by Western blotting and immunohistochemistry. The expression of ERα and ERβ was correlated with the expression of activated NF-κB, activated IKK and cyclin D1 by Spearman's correlation. RESULTS Both ER subtypes were expressed in normal livers but male livers showed significantly higher expression of ERα than females(P < 0.05). We observed significantly higher m RNA expression of ERα in HCV-related HCC liver tissues as compared to normals(P < 0.05) and ERβ in livers of HCV-related cirrhosis and HCV-related HCC subjects(P < 0.05). At the protein level, there was a significantly higher expression of nuclear ERα in livers of HCV-related HCC patients and nuclear ERβ in HCV-related cirrhosis patients as compared to normals(P < 0.05). Furthermore, we observed a significantly higher expression of phosphorylated NF-κB and cyclin D1 in diseased livers(P < 0.05). There was a positive correlation between the expression of nuclear ER subtypes and nuclear cyclin D1 and a negative correlation between cytoplasmic ER subtypes and cytoplasmic phosphorylated IKK in HCV-related HCC livers. These findings suggest that dysregulated expression of ER subtypes following chronic HCVinfection may contribute to the progression of HCVrelated cirrhosis to HCV-related HCC.CONCLUSION Gender differences were observed in ERα expression in normal livers. Alterations in ER subtype expression observed in diseased livers may influence genderrelated disparity in HCV-related pathogenesis.
