Estrogen Receptor Alpha Expression in Podocytes Mediates Protection against Apoptosis In-Vitro and In-Vivo

Estrogen receptor alpha (ERα) has been recognized now for several decades as playing a key role in reproduction and exerting functions in numerous nonreproductive tissues. In this review, we attempt to summarize the in vitro studies that are the basis of our current understanding of the mechanisms of action of ERα as a nuclear receptor and the key roles played by its two activation functions (AFs) in its transcriptional activities. We then depict the consequences of the selective inactivation of these AFs in mouse models, focusing on the prominent roles played by ERα in the reproductive tract and in the vascular system. Evidence has accumulated over the two last decades that ERα is also associated with the plasma membrane and activates non-nuclear signaling from this site. These rapid/nongenomic/membrane-initiated steroid signals (MISS) have been characterized in a variety of cell lines, and in particular in endothelial cells. The development of selective pharmacological tools that specifically activate MISS and the generation of mice expressing an ERα protein impeded for membrane localization have begun to unravel the physiological role of MISS in vivo. Finally, we discuss novel perspectives for the design of tissue-selective ER modulators based on the integration of the physiological and pathophysiological roles of MISS actions of estrogens.

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Expression of aromatase and estrogen receptor alpha in chondrosarcoma, but no beneficial effect of inhibiting estrogen signaling both in vitro and in vivo

Clinical Sarcoma Research ◽

10.1186/2045-3329-1-5 ◽

2011 ◽

Vol 1 (1) ◽

pp. 5 ◽

Cited By ~ 22

Author(s):

Danielle Meijer ◽

Hans Gelderblom ◽

Marcel Karperien ◽

Anne-Marie Cleton-Jansen ◽

Pancras CW Hogendoorn ◽

...

Keyword(s):

Estrogen Receptor ◽

Beneficial Effect ◽

Estrogen Receptor Alpha ◽

Estrogen Signaling ◽

Receptor Alpha

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Estrogen Receptor Alpha Prevents Bladder Cancer Development via INPP4B inhibited Akt Pathway in vitro and in vivo

Oncotarget ◽

10.18632/oncotarget.1421 ◽

2014 ◽

Vol 5 (17) ◽

pp. 7917-7935 ◽

Cited By ~ 35

Author(s):

Iawen Hsu ◽

Chiuan-Ren Yeh ◽

Spencer Slavin ◽

Hiroshi Miyamoto ◽

George J. Netto ◽

...

Keyword(s):

Bladder Cancer ◽

Estrogen Receptor ◽

Estrogen Receptor Alpha ◽

Cancer Development ◽

Akt Pathway ◽

Receptor Alpha

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BCAS2 Enhances Carcinogenic Effects of Estrogen Receptor Alpha in Breast Cancer Cells

International Journal of Molecular Sciences ◽

10.3390/ijms20040966 ◽

2019 ◽

Vol 20 (4) ◽

pp. 966 ◽

Cited By ~ 2

Author(s):

Ángel Salmerón-Hernández ◽

María Noriega-Reyes ◽

Albert Jordan ◽

Noemi Baranda-Avila ◽

Elizabeth Langley

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Cancer Cells ◽

Transcriptional Activation ◽

Cancer Biology ◽

Breast Cancer Cells ◽

Estrogen Receptor Alpha ◽

Receptor Alpha

Estrogen receptor alpha (ERα) has an established role in breast cancer biology. Transcriptional activation by ERα is a multistep process modulated by coactivator and corepressor proteins. Breast Cancer Amplified Sequence 2 (BCAS2), is a poorly studied ERα coactivator. In this work, we characterize some of the mechanisms through which this protein increases ERα activity and how this promotes carcinogenic processes in breast cancer cells. Using protein-protein interaction and luciferase assays we show that BCAS2 interacts with ERα both in vitro and in vivo and upregulates transcriptional activation of ERα directly through its N-terminal region (AF-1) and indirectly through its C-terminal (AF-2) region, acting in concert with AF-2 interacting coactivators. Elevated expression of BCAS2 positively affects proliferation, clonogenicity and migration of breast cancer cells and directly activates ERα regulated genes which have been shown to play a role in tumor growth and progression. Finally, we used signal transduction pathway inhibitors to elucidate how BCAS2 is regulated in these cells and observed that BCAS2 is preferentially regulated by the PI3K/AKT signaling pathway. BCAS2 is an AF-1 coactivator of ERα whose overexpression promotes carcinogenic processes, suggesting an important role in the development of estrogen-receptor positive breast cancer.

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Development of a Graphical User Interface Application to Identify Marginal and Potent Ligands for Estrogen Receptor Alpha

Indonesian Journal of Chemistry ◽

10.22146/ijc.34561 ◽

2019 ◽

Vol 19 (2) ◽

pp. 531 ◽

Cited By ~ 1

Author(s):

Nunung Yuniarti ◽

Sudi Mungkasi ◽

Sri Hartati Yuliani ◽

Enade Perdana Istyastono

Keyword(s):

Estrogen Receptor ◽

User Interface ◽

Graphical User Interface ◽

Estrogen Receptor Alpha ◽

Predictive Ability ◽

In Vitro Test ◽

Ligand Interaction ◽

Qsar Analysis ◽

Receptor Alpha

Employing ensemble Protein-Ligand Interaction Fingerprints (ensPLIF) as descriptors in post retrospective Structure-Based Virtual Screening (SBVS) campaigns Quantitative Structure-Activity Relationship (QSAR) analysis has been proven to significantly increase the predictive ability in the identification of potent ligands for estrogen receptor alpha (ERα). In the research presented in this article, similar approaches have been performed to construct and retrospectively validate an SBVS protocol to identify marginal ligands for ERα. Based on both validated SBVS protocols, a graphical-user-interface (GUI) application to identify if a compound is a non-, moderate or potent ligand for ERα was developed. The GUI application was subsequently used to virtually screen genistin, genistein, daidzin, and daidzein, followed by in vitro test employing a cytotoxic assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method.

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Activation of Penile Proadipogenic Peroxisome Proliferator-Activated Receptor with an Estrogen: Interaction with Estrogen Receptor Alpha during Postnatal Development

PPAR Research ◽

10.1155/2008/651419 ◽

2008 ◽

Vol 2008 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Mahmoud M. Mansour ◽

Hari O. Goyal ◽

Tim D. Braden ◽

John C. Dennis ◽

Dean D. Schwartz ◽

...

Keyword(s):

Estrogen Receptor ◽

Estrogen Receptor Alpha ◽

Corpus Cavernosum ◽

Cellular Level ◽

Transitional Epithelium ◽

Peroxisome Proliferator ◽

Sprague Dawley ◽

Peroxisome Proliferator Activated Receptor ◽

Receptor Alpha

Exposure to the estrogen receptor alpha (ER) ligand diethylstilbesterol (DES) between neonatal days 2 to 12 induces penile adipogenesis and adult infertility in rats. The objective of this study was to investigate the in vivo interaction between DES-activated ER and the proadipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPAR). Transcripts for PPARs , , and and 1a splice variant were detected in Sprague-Dawley normal rat penis with PPAR predominating. In addition, PPAR1b and PPAR2 were newly induced by DES. The PPAR transcripts were significantly upregulated with DES and reduced by antiestrogen ICI 182, 780. At the cellular level, PPAR protein was detected in urethral transitional epithelium and stromal, endothelial, neuronal, and smooth muscular cells. Treatment with DES activated ER and induced adipocyte differentiation in corpus cavernosum penis. Those adipocytes exhibited strong nuclear PPAR expression. These results suggest a biological overlap between PPAR and ER and highlight a mechanism for endocrine disruption.

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MP34-02 ESTROGEN RECEPTOR ALPHA PREVENTS BLADDER CANCER VIA INPP4B/AKT PATHWAY: IN VIVO KNOCKOUT MOUSE EVIDENCE AND HUMAN TISSUE ANALYSIS

The Journal of Urology ◽

10.1016/j.juro.2014.02.1015 ◽

2014 ◽

Vol 191 (4S) ◽

Author(s):

Chiuan-Ren Yeh ◽

Iawen Hsu ◽

Spencer Slavin ◽

Chawnshang Chang ◽

Edward M. Messing ◽

...

Keyword(s):

Bladder Cancer ◽

Estrogen Receptor ◽

Human Tissue ◽

Knockout Mouse ◽

Estrogen Receptor Alpha ◽

Akt Pathway ◽

Tissue Analysis ◽

Receptor Alpha

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The AF-1 activation function of estrogen receptor alpha is necessary and sufficient for uterine epithelial cell proliferation in vivo

Annales d Endocrinologie ◽

10.1016/j.ando.2013.07.096 ◽

2013 ◽

Vol 74 (4) ◽

pp. 265-266

Author(s):

A. Abot ◽

C. Fontaine ◽

P. Gourdy ◽

F. Lenfant ◽

J.F. Arnal

Keyword(s):

Cell Proliferation ◽

Estrogen Receptor ◽

Epithelial Cell ◽

Estrogen Receptor Alpha ◽

Activation Function ◽

Epithelial Cell Proliferation ◽

Uterine Epithelial Cell ◽

Receptor Alpha ◽

Necessary And Sufficient

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Computer-Aided Drug Repurposing: A Cyclooxygenase-2 Inhibitor Celecoxib as a Ligand for Estrogen Receptor Alpha

Indonesian Journal of Chemistry ◽

10.22146/ijc.21196 ◽

2015 ◽

Vol 15 (3) ◽

pp. 274-280 ◽

Cited By ~ 3

Author(s):

Enade Perdana Istyastono ◽

Florentinus Dika Octa Riswanto ◽

Sri Hartati Yuliani

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

In Silico ◽

Estrogen Receptor Alpha ◽

Cyclooxygenase 2 ◽

Cytotoxic Activities ◽

In Vitro Test ◽

Receptor Alpha ◽

Vitro Test

A cyclooxygenase-2 (COX-2) inhibitor celecoxib has been previously reported to have cytotoxic activities towards gastric, prostate, ovarian, colon and breast cancer cell lines. This article reports that the cytotoxic activities of celecoxib could be resulted from its activity as a potent ligand for estrogen receptor alpha (ERα). Aided by molecular docking simulations, an in silico test to examine whether celecoxib is a ligand for estrogen receptor alpha (ERα) was performed followed by in vitro test employing cytotoxic assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method. The compound was extracted from Celebrex®. Measured by using UV spectrophotometric method at 255.5 nm, it was identified that the content of celecoxib was 102.15 mg/271.48 mg capsule content. The in silico test indicated that celecoxib is a potent ligand for ERα. This finding was confirmed experimentally by an in vitro test that celecoxib has a comparable activity as an ERα ligand to tamoxifen, a drug of choice for breast cancer treatment.

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