Effects of (R,S)/(S,R)-4,5-bis(2-chloro-4-hydroxyphenyl)-2-imidazolines and (R,S)/(S,R)-2,3-bis(2-chloro-4-hydroxyphenyl)piperazines on estrogen receptor alpha level and transcriptional activity in MCF-7 cells

2007 ◽  
Vol 74 (7) ◽  
pp. 1029-1038 ◽  
Author(s):  
Ioanna Laïos ◽  
Anny Cleeren ◽  
Guy Leclercq ◽  
Denis Nonclercq ◽  
Guy Laurent ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Transcriptional Activity ◽  
Receptor Alpha ◽  
Alpha Level ◽  
Mcf 7

scholarly journals Estrogen receptor alpha mediates neuronal differentiation and neuroprotection in PC12 cells: critical role of the A/B domain of the receptor

2005 ◽  
Vol 35 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Yohann Mérot ◽  
François Ferrière ◽  
Edith Debroas ◽  
Gilles Flouriot ◽  
Dominique Duval ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Neuronal Differentiation ◽  
Pc12 Cells ◽  
Estrogen Receptor Alpha ◽  
Transcriptional Activity ◽  
Target Genes ◽  
Critical Role ◽  
Full Length ◽  
Receptor Alpha ◽  
Estrogenic Effects

Numerous studies, both in vivo and in vitro, have reported neuronal differentiating and neuroprotective actions of estrogens. Most of these estrogenic effects are mediated through specific receptors termed estrogen receptors. The aim of this study was to assess the importance of the N-terminal A/B domain of the estrogen receptor-alpha (ERα) in its neuronal aspects. Consequently, estrogen effects on (i) the transcriptional activity of target genes, (ii) neuronal differentiation and (iii) neuroprotection in PC12 cells transfected with either a full length form of ERα or an A/B domain truncated form (ERαCF), have been studied. We demonstrate that the maximal estrogen-induced transcriptional activity of reporter genes requires a full length ERα, especially when cells are differentiated. Precisely, the transcriptional activity of ERα in differentiated cells relies, predominantly, on the activation function AF-1, located in the A/B domain. Furthermore, in PC12 cells stably expressing ERα, 17β-estradiol markedly enhances the neurite outgrowth triggered by treatment with nerve growth factor and protects cells from oxidative shocks induced by depletion of glutathione. These estrogenic effects are not observed in non-transfected cells and in cells transfected with the truncated ER, devoid of the A/B domain. Altogether, these results underline the importance of the A/B domain of ERα in both the differentiating and the neuroprotective effects of estrogens.

In silico Molecular Modelling of Selected Natural Ligands and their Binding Features with Estrogen Receptor Alpha

2018 ◽  
Vol 15 (1) ◽  
pp. 89-96 ◽  
Author(s):  
V.L. Maruthanila ◽  
R. Elancheran ◽  
Nand Kishor Roy ◽  
Anupam Bhattacharya ◽  
Ajaikumar B. Kunnumakkara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cell Line ◽  
In Silico ◽  
Estrogen Receptor Alpha ◽  
Natural Compounds ◽  
Pharmacokinetic Parameters ◽  
Anticancer Activities ◽  
Receptor Alpha ◽  
Mcf 7

Background: Breast cancer is one of the most common cancers diagnosed among women. It is now recognized that two receptors mediate estrogen action and the presence of estrogen receptor alpha (ER&#945;) correlates with better prognosis and the likelihood of response to hormonal therapy. ER&#945; is an attractive target for the treatment of breast cancer. Most of the drugs currently used for the breast cancer treatment have numerous side effects and they are often unsuccessful in removing the tumour completely. Hence, we focused on natural compounds like flavonoids, polyphenols, etc. which do not exhibit any high toxic effects against normal cells. </P><P> Objectives: To identify the potential natural inhibitors for BCa through an optimised in silico approach. </P><P> Methods: Structural modification and molecular docking-based screening approaches were imposed to identify the novel natural compounds by using Schrödinger (Maestro 9.5). The Qikprop v3.5 was used for the evaluation of important ADME parameters and its permissible ranges. Cytotoxicity of the compounds was evaluated by MTT assay against MCF-7 Cell lines. Results: From the docking studies, we found that the compounds, Myricetin, Quercetin, Apigenin, Luteolin and Baicalein showed the highest Glide Scores -10.78, -9.48, -8.92, -8.87 and -8.82 kcal mol-1 respectively. Of these, Luteolin and Baicalein showed the significant IC50 values (25 &#177; 4.0 and 58.3 &#177; 4.4 &#181;M, respectively) against MCF-7 cell line. The ADME profiling of the test compounds was evaluated to find the drug-likeness and pharmacokinetic parameters. We mainly focused on in silico study to dock the compounds into the human estrogen receptor ligand binding domain (hERLBD) and compare their predicted binding affinity with known antiestrogens. Myricetin, Quercetin, Apigenin, Luteolin and Baicalein were identified as the most promising among all. Of these, Luteolin and Baicalein showed significant anticancer activities against MCF-7 cell line. These findings may provide basic information for the development of anti-breast cancer agents.

scholarly journals Alternatively Constructed Estrogen Receptor Alpha-Driven Super-Enhancers Result in Similar Gene Expression in Breast and Endometrial Cell Lines

2020 ◽  
Vol 21 (5) ◽  
pp. 1630 ◽  
Author(s):  
Dóra Bojcsuk ◽  
Gergely Nagy ◽  
Bálint László Bálint
Keyword(s):  
Estrogen Receptor ◽  
Cell Lines ◽  
Estrogen Receptor Alpha ◽  
Receptor Alpha ◽  
Highly Active ◽  
Ishikawa Cells ◽  
Cell Type Specific ◽  
The Individual ◽  
Similar Gene ◽  
Mcf 7

Super-enhancers (SEs) are clusters of highly active enhancers, regulating cell type-specific and disease-related genes, including oncogenes. The individual regulatory regions within SEs might be simultaneously bound by different transcription factors (TFs) and co-regulators, which together establish a chromatin environment conducting to effective transcription. While cells with distinct TF profiles can have different functions, how different cells control overlapping genetic programs remains a question. In this paper, we show that the construction of estrogen receptor alpha-driven SEs is tissue-specific, both collaborating TFs and the active SE components greatly differ between human breast cancer-derived MCF-7 and endometrial cancer-derived Ishikawa cells; nonetheless, SEs common to both cell lines have similar transcriptional outputs. These results delineate that despite the existence of a combinatorial code allowing alternative SE construction, a single master regulator might be able to determine the overall activity of SEs.

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