Mus musculus
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ABSTRACT:
PROVIDER: PRJNA99829 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Estrogen clearly prevents osteoporotic bone loss by attenuating bone resorption. The molecular basis of how this is accomplished, however, remains elusive. Here we report a critical role of osteoclastic ERa in mediating estrogen action on bone in females. We selectively ablated ERa in differentiated osteoclasts (ERa dOc/dOc). ERa dOc/dOc females, but not males, exhibited clear trabecular bone loss, similar to the osteoporotic bone phenotype in post-menopausal women. Recovery of bone loss by estrogen treatment of the ovariectomized ERa dOc/dOc females was ineffective in the trabecular areas of the long bones and lumbar vertebral bodies. Osteoclastic apoptosis, induced by estrogen, occurred simultaneously with up-regulation of Fas ligand (FasL) expression in intact trabecular bones of ERa +/+mice, but not in ERa dOc/dOc mice. ERa was also required for similar effects of estrogen and tamoxifen in cultured osteoclasts. These findings suggest that the osteoprotective actions of estrogen and SERMS are mediated at least in part through osteoclastic ERa in trabecular bone; and the life span of mature osteoclasts is regulated through activation of the Fas/FasL system. Experiment Overall Design: Wild type and osteoclast-specific Estrogen Receptor alpha knock-out mice were ovariectomized. The number of both genotypes of mice was eight. The mice of each genotypes were divided to vehicle control and estrogen treated group. Four hours after chemical treatment, the distal 5 mm of the left femurs were harvested after sacrificing by cervical dislocation and total RNAs were purified for Affymetix GeneChip microarray analysis without pooling. Therefore, this experiment consists of four groups with four replicates per group.
2008-06-15 | E-GEOD-7798 | biostudies-arrayexpress
Project description:Estrogen clearly prevents osteoporotic bone loss by attenuating bone resorption. The molecular basis of how this is accomplished, however, remains elusive. Here we report a critical role of osteoclastic ERa in mediating estrogen action on bone in females. We selectively ablated ERa in differentiated osteoclasts (ERa dOc/dOc). ERa dOc/dOc females, but not males, exhibited clear trabecular bone loss, similar to the osteoporotic bone phenotype in post-menopausal women. Recovery of bone loss by estrogen treatment of the ovariectomized ERa dOc/dOc females was ineffective in the trabecular areas of the long bones and lumbar vertebral bodies. Osteoclastic apoptosis, induced by estrogen, occurred simultaneously with up-regulation of Fas ligand (FasL) expression in intact trabecular bones of ERa +/+mice, but not in ERa dOc/dOc mice. ERa was also required for similar effects of estrogen and tamoxifen in cultured osteoclasts. These findings suggest that the osteoprotective actions of estrogen and SERMS are mediated at least in part through osteoclastic ERa in trabecular bone; and the life span of mature osteoclasts is regulated through activation of the Fas/FasL system. Keywords: Study about estrogen response of osteoclast-specific estrogen receptor alpha mice
2007-06-01 | GSE7798 | GEO
Project description:Estrogen Receptor alpha (ERα) is a ligand-inducible transcription factor that mediates estrogen signaling in hormone-responsive breast cancer (BC) and is the primary target of specific anticancer therapies that although effective can generate resistance phenomena that represents a crucial problem in clinical management of patients affected by this disease. DOT1 Like Histone Lysine Methyltransferase (DOT1L) and Menin 1 (MEN1) have been identified as functional component of the ERα mechanism of action. To investigate the involvement of DOT1L and MEN1 in mediating ERα actions in hormone-responsive and endocrine-resistant BC, interaction proteomics was applied to map the DOT1l and MEN1 nuclear interacting partners in MCF7 breast cancer cell nuclei in order to the identifiy new possible therapeutic targets for a more effective pharmacological treatment of endocrine therapy-resistant tumors.
2022-08-12 | PXD026864 | Pride
Project description:Estrogen Receptor alpha (ERα) is a ligand-inducible transcription factor that mediates estrogen signaling in hormone-responsive breast cancer (BC) and is the primary target of specific anticancer therapies. Although ERα blockade with these drugs is effective, the development of a resistance to treatment represents the key problem in clinical management of patients affected by this disease. Understanding the molecular mechanisms underlying ERα action in BC cells may help the identification of new therapeutic targets for more effective pharmacological treatment of endocrine therapy-resistant tumors. We recently discovered the epigenetic enzyme DOT1L (DOT1 Like Histone Lysine Methyltransferase) as a novel nuclear partner of ERα in BC cells. To investigate the involvement of DOT1L in mediating ERα actions in hormone-responsive and endocrine-resistant BC, physical and functional interaction between these two molecules on chromatin was mapped by Chromatin Immunoprecipitation coupled to Mass Spectrometry (ChIP-MS).
2019-02-09 | PXD010314 | Pride
Project description:The Estrogen Receptor alpha (ERα), is a member of the nuclear receptor superfamily of trancriptional regulators that mediates estrogen signaling in hormone-responsive tumors controlling key cellular functions by assembling in large functional multiprotein complexes. Interaction proteomics coupled to mass spectrometry (MS) was applied to deeply characterize the nuclear interactors partners whom association with the receptor is mediated by RNAs
2019-07-29 | PXD012630 | Pride
Project description:Fas ligand (FasL)/TNFSF6, a member of the tumor necrosis factor (TNF) superfamily, can promote apoptosis in activated primary B cells, T cells, dendritic cells, and synovial fibroblasts through Fas and is involved in the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA). Meanwhile, decoy receptor 3 (DcR3) competitively binds soluble FasL in addition to TL1A and LIGHT and inhibits the signaling of FasL via Fas. Therefore, FasL-DcR3/Fas signaling may be involved in the pathogenesis of RA. We hypothesized that FasL regulates the gene expression in RA-FLS. We used to search for genes in which expression in RA-FLS is regulated by FasL.
2020-06-30 | GSE153378 | GEO
Project description:Active estrogen receptor-alpha signaling in ovarian cancer
| PRJNA322076 | ENA
Project description:Estrogen receptor alpha (ERα) is a ligand dependent transcription regulator, which contains two transactivation functional domains, AF-1 and AF-2. These activities are regulated differently by the ligands. Specifically, the selective estrogen receptor modulators (SERMs) regulate AF-1 rather than AF-2. It is important to know whether AF-1/AF-2 predominantly regulated genes exist in the tissues for a better understanding of the SERMs functionality. We sought out AF-1 dependent estrogenic genes by using the AF-2 mutated knock-in (KI) mouse model, AF2ERKI. AF2ER is an estrogen-insensitive AF-2 disrupted ERα mutant mouse but unique to this model, AF-1 can be activated by the estrogen-antagonists, such as fulvestrant (ICI) and 4-hydroxytamoxifen (Tam) in vitro and in vivo. The information of genome-wide ICI or Tam dependent AF-2 mutated ERα binding sites could explain the mechanism of the selective estrogenic action of SERMs through AF-1 dependent gene regulation.
2019-12-10 | GSE137196 | GEO
Project description:The nuclear hormone receptor, estrogen receptor-alpha (ERα), and MAP kinases both play key roles in hormone-dependent cancers, yet their interplay and the integration of their signaling inputs remain poorly understood. In these studies, we document that estrogen-occupied ERα activates and interacts with ERK2, a downstream effector in the MAPK pathway, resulting in ERK2 and ERα colocalization at chromatin binding sites across the genome of breast cancer cells. KEYWORDS: siRNA knock-down, ligand treatment
2011-01-10 | GSE24592 | GEO
Project description:TNF-like ligand 1A (TL1A) is a member of TNF receptor superfamily and involved in the pathogenesis of autoimmune diseases by inducing apoptosis via intracellular death domain or promoting inflammation through the activation of NFκB by binding to its specific receptor death receptor 3 (DR3). Meanwhile, decoy receptor 3 (DcR3) competitively binds soluble TL1A in addition to Fas-ligand (FasL) and LIGHT and inhibits the signaling of TL1A via DR3. DcR3 overexpressed in rheumatoid synovial fibroblasts (RA-FLS) stimulated with inflammatory cytokines such as TNFα or IL-1β inhibits Fas-induced apoptosis. In contrast, DcR3 inhibited cell proliferation induced by inflammatory cytokines via membrane-bound TL1A expressed on RA-FLS. Therefore, TL1A-DcR3/DR3 signaling may be involved in the pathogenesis of RA by modulating apoptosis and proliferation of RA-FLS. We hypothesized that TL1A regulates the gene expression in RA-FLS. We used to search for genes in which expression in RA-FLS is regulated by the ligation of TL1A.
2014-12-10 | GSE63995 | GEO