Dataset Information

Estrogen Receptor ? Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis.

ABSTRACT: Alterations in estrogen-mediated cellular signaling play an essential role in the pathogenesis of endometriosis. In addition to higher estrogen receptor (ER) ? levels, enhanced ER? activity was detected in endometriotic tissues, and the inhibition of enhanced ER? activity by an ER?-selective antagonist suppressed mouse ectopic lesion growth. Notably, gain of ER? function stimulated the progression of endometriosis. As a mechanism to evade endogenous immune surveillance for cell survival, ER? interacts with cellular apoptotic machinery in the cytoplasm to inhibit TNF-?-induced apoptosis. ER? also interacts with components of the cytoplasmic inflammasome to increase interleukin-1? and thus enhance its cellular adhesion and proliferation properties. Furthermore, this gain of ER? function enhances epithelial-mesenchymal transition signaling, thereby increasing the invasion activity of endometriotic tissues for establishment of ectopic lesions. Collectively, we reveal how endometrial tissue generated by retrograde menstruation can escape immune surveillance and develop into sustained ectopic lesions via gain of ER? function.

SUBMITTER: Han SJ

PROVIDER: S-EPMC4640214 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Estrogen Receptor β Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis.

Han Sang Jun SJ Jung Sung Yun SY Wu San-Pin SP Hawkins Shannon M SM Park Mi Jin MJ Kyo Satoru S Qin Jun J Lydon John P JP Tsai Sophia Y SY Tsai Ming-Jer MJ DeMayo Francesco J FJ O'Malley Bert W BW

Cell 20151101 4

Alterations in estrogen-mediated cellular signaling play an essential role in the pathogenesis of endometriosis. In addition to higher estrogen receptor (ER) β levels, enhanced ERβ activity was detected in endometriotic tissues, and the inhibition of enhanced ERβ activity by an ERβ-selective antagonist suppressed mouse ectopic lesion growth. Notably, gain of ERβ function stimulated the progression of endometriosis. As a mechanism to evade endogenous immune surveillance for cell survival, ERβ int ...[more]

PMID: 26544941

Similar Datasets

Project description:BackgroundMany epidemiological studies have suggested an association between estrogen receptor-beta (ER-β) polymorphisms with endometriosis risk. However, the results of these studies have been inconsistent. In the present study, we performed a meta-analysis to clarify the associations between the ER-β rs4986938 and rs1256049 polymorphisms and endometriosis risk.MethodsEligible publications were retrieved from the PubMed, ISI Web of Science, and several Chinese language databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random or fixed effect model.ResultsA total of eight studies (1100 cases/1485 controls) for the rs4986938 polymorphism and four studies (353 cases/450 controls) for the rs1256049 polymorphism were included in this meta-analysis. Regarding the rs4986938 polymorphism, no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis. In the subgroup analyses by ethnicity, study sample size, endometriosis-associated infertility, and stage of endometriosis, a significantly increased risk was observed among mixed populations (dominant model, OR=2.03, 95% CI=1.56-2.64) and among cases with endometriosis-associated infertility (dominant model, OR=1.83, 95% CI=1.26-2.67). Regarding the rs1256049 polymorphism, no obvious associations were found for all genetic models in the overall population. Subgroup analyses by ethnicity and study sample size revealed that only one study of a mixed population with small sample size showed an increased risk of endometriosis. No publication bias was found in the present study.ConclusionsThe results of this meta-analysis suggest that the ER-β rs4986938 and rs1256049 polymorphisms may not be associated with endometriosis risk, while the observed increased risk of endometriosis-associated infertility may be due to bias by the inclusion of small-scale studies.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_184.

Project description:Recent researches have shown that estrogen receptor-β (ERβ) activator may be a potent anticancer agent for prostate cancer (PCa), and our previous study also indicated that dioscin can upregulate the expression of ERβ in MC3T3-E1 cell. In the present work, the activity and mechanism of dioscin, a natural product, against PCa were investigated. The results showed that dioscin markedly inhibited cell viability, colony formation, motility and induced apoptosis in PC3 cells. Moreover, dioscin disrupted the formation of PC3 cell-derived mammospheres and reduced aldehyde dehydrogenase (ALDH) level and the CD133+/CD44+ cells, indicating that dioscin had a potent inhibitory activity on prostate cancer stem cells (PCSCs). In vivo results also showed that dioscin significantly suppressed the tumor growth of PC3 cell xenografts in nude mice. Furthermore, mechanism investigation showed that dioscin markedly upregulated ERβ expression level, subsequently increased prolyl hydroxylase 2 level, decreased the levels of hypoxia-inducible factor-1α, vascular endothelial growth factor A and BMI-1, and thus induced cell apoptosis by regulating the expression levels of caspase-3 and Bcl-2 family proteins. In addition, transfection experiment of ERβ-siRNA further indicated that diosicn showed excellent activity against PCa in vitro and in vivo by increasing ERβ expression level. The co-immunoprecipitation (Co-IP) results further suggested that dioscin promoted the interaction of c-ABL and ERβ, but did not change c-ABL expression. Moreover, the molecular docking assay showed that dioscin processed powerful affinity toward to ERβ mainly through the strong hydrogen bonding and hydrophobic effects, and the actions of dioscin on ERβ activation and tumor cells inhibition were significantly weakened in the mutational (Phe-336, Phe-468) PC3 cells. Collectively, these findings proved that dioscin exerted efficient anti-PCa activity via activation of ERβ, which should be developed as an efficient candidate in clinical for treating this cancer in the future.

Dataset Information

Estrogen Receptor ? Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis.

Publications

Estrogen Receptor β Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets