In vitro studies revealed a downregulation of Wnt/β-catenin cascade by active vitamin D and TX 527 analog in a Kaposi's sarcoma cellular model
| Autor: | Pablo De Genaro, Alejandra Suares, Verónica González-Pardo, Cinthya Tapia |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
NEOPLASM Down-Regulation B-CATENIN Toxicology Calcitriol receptor Models Biological VGPCR Cell Line Receptors G-Protein-Coupled Ciencias Biológicas 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation Antigens CD medicine Animals RNA Messenger RNA Small Interfering Receptor Kaposi's sarcoma Sarcoma Kaposi Wnt Signaling Pathway beta Catenin Cholecalciferol Gene knockdown Chemistry Wnt signaling pathway General Medicine Bioquímica y Biología Molecular medicine.disease Cadherins Molecular biology VITAMIN D 030104 developmental biology 030220 oncology & carcinogenesis Catenin Alkynes Intercellular Signaling Peptides and Proteins Receptors Calcitriol Signal transduction CIENCIAS NATURALES Y EXACTAS |
| Zdroj: | Toxicology in vitro : an international journal published in association with BIBRA. 63 |
| ISSN: | 1879-3177 |
| Popis: | The Kaposi´s sarcoma-associated herpesvirus G-protein-coupled receptor (vGPCR) is a key molecule in the pathogenesis of Kaposi´s sarcoma. We have previously demonstrated that 1α,25(OH)2D3 or its less calcemic analogTX 527 exerts antiproliferative effects in endothelial cells stable expressing vGPCR. Since it is well documentedthat vGPCR activates the canonical Wnt/β-catenin signaling pathway, the aim of this study was to evaluate ifWnt/β-catenin cascade is target of 1α,25(OH)2D3 or TX 527 as part of their antineoplastic mechanism. Firstly,Western blot studies showed an increase in β-catenin protein levels in a dose and time dependent manner; andwhen VDR was knockdown, β-catenin protein levels were significantly decreased. Secondly, β-catenin localization, investigated by immunofluorescence and subcellular fractionation techniques, was found increased in thenucleus and plasma membrane after 1α,25(OH)2D3 treatment. VE-cadherin protein levels were also increased inthe plasma membrane fraction. Furthermore, β-catenin interaction with VDR was observed by co-immunoprecipitation and mRNA expression of β-catenin target genes was found decreased. Finally, DKK-1, theextracellular inhibitor of Wnt/β-catenin pathway, showed an initial upregulation of mRNA expression.Altogether, the results obtained by different techniques revealed a downregulation of Wnt/β-catenin cascadeafter 1α,25(OH)2D3 or TX 527 treatment, showing the foundation for a potential chemotherapeutic agent. Fil: Tapia, Cinthya Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina Fil: Suares, Alejandra Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina Fil: de Genaro, Pablo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina Fil: González Pardo, María Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina |
| Databáze: | OpenAIRE |
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