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Analysis of Activated Platelet-Derived Growth Factor β Receptor and Ras-MAP Kinase Pathway in Equine Sarcoid Fibroblasts

Equine sarcoids are skin tumours of fibroblastic origin affecting equids worldwide. Bovine papillomavirus type-1 (BPV-1) and, less commonly, type-2 are recognized as etiological factors of sarcoids. The transforming activity of BPV is related to the functions of its major oncoprotein E5 which binds...

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Autores principales: Altamura, Gennaro, Corteggio, Annunziata, Nasir, Lubna, Yuan, Zheng Qiang, Roperto, Franco, Borzacchiello, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726019/
https://www.ncbi.nlm.nih.gov/pubmed/23936786
http://dx.doi.org/10.1155/2013/283985
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author Altamura, Gennaro
Corteggio, Annunziata
Nasir, Lubna
Yuan, Zheng Qiang
Roperto, Franco
Borzacchiello, Giuseppe
author_facet Altamura, Gennaro
Corteggio, Annunziata
Nasir, Lubna
Yuan, Zheng Qiang
Roperto, Franco
Borzacchiello, Giuseppe
author_sort Altamura, Gennaro
collection PubMed
description Equine sarcoids are skin tumours of fibroblastic origin affecting equids worldwide. Bovine papillomavirus type-1 (BPV-1) and, less commonly, type-2 are recognized as etiological factors of sarcoids. The transforming activity of BPV is related to the functions of its major oncoprotein E5 which binds to the platelet-derived growth factor β receptor (PDGFβR) causing its phosphorylation and activation. In this study, we demonstrate, by coimmunoprecipitation and immunoblotting, that in equine sarcoid derived cell lines PDGFβR is phosphorylated and binds downstream molecules related to Ras-mitogen-activated protein kinase-ERK pathway thus resulting in Ras activation. Imatinib mesylate is a tyrosine kinase receptors inhibitor which selectively inhibits the activation of PDGFβR in the treatment of several human and animal cancers. Here we show that imatinib inhibits receptor phosphorylation, and cell viability assays demonstrate that this drug decreases sarcoid fibroblasts viability in a dose-dependent manner. This study contributes to a better understanding of the molecular mechanisms involved in the pathology of sarcoids and paves the way to a new therapeutic approach for the treatment of this common equine skin neoplasm.
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spelling pubmed-37260192013-08-09 Analysis of Activated Platelet-Derived Growth Factor β Receptor and Ras-MAP Kinase Pathway in Equine Sarcoid Fibroblasts Altamura, Gennaro Corteggio, Annunziata Nasir, Lubna Yuan, Zheng Qiang Roperto, Franco Borzacchiello, Giuseppe Biomed Res Int Research Article Equine sarcoids are skin tumours of fibroblastic origin affecting equids worldwide. Bovine papillomavirus type-1 (BPV-1) and, less commonly, type-2 are recognized as etiological factors of sarcoids. The transforming activity of BPV is related to the functions of its major oncoprotein E5 which binds to the platelet-derived growth factor β receptor (PDGFβR) causing its phosphorylation and activation. In this study, we demonstrate, by coimmunoprecipitation and immunoblotting, that in equine sarcoid derived cell lines PDGFβR is phosphorylated and binds downstream molecules related to Ras-mitogen-activated protein kinase-ERK pathway thus resulting in Ras activation. Imatinib mesylate is a tyrosine kinase receptors inhibitor which selectively inhibits the activation of PDGFβR in the treatment of several human and animal cancers. Here we show that imatinib inhibits receptor phosphorylation, and cell viability assays demonstrate that this drug decreases sarcoid fibroblasts viability in a dose-dependent manner. This study contributes to a better understanding of the molecular mechanisms involved in the pathology of sarcoids and paves the way to a new therapeutic approach for the treatment of this common equine skin neoplasm. Hindawi Publishing Corporation 2013 2013-07-11 /pmc/articles/PMC3726019/ /pubmed/23936786 http://dx.doi.org/10.1155/2013/283985 Text en Copyright © 2013 Gennaro Altamura et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Altamura, Gennaro
Corteggio, Annunziata
Nasir, Lubna
Yuan, Zheng Qiang
Roperto, Franco
Borzacchiello, Giuseppe
Analysis of Activated Platelet-Derived Growth Factor β Receptor and Ras-MAP Kinase Pathway in Equine Sarcoid Fibroblasts
title Analysis of Activated Platelet-Derived Growth Factor β Receptor and Ras-MAP Kinase Pathway in Equine Sarcoid Fibroblasts
title_full Analysis of Activated Platelet-Derived Growth Factor β Receptor and Ras-MAP Kinase Pathway in Equine Sarcoid Fibroblasts
title_fullStr Analysis of Activated Platelet-Derived Growth Factor β Receptor and Ras-MAP Kinase Pathway in Equine Sarcoid Fibroblasts
title_full_unstemmed Analysis of Activated Platelet-Derived Growth Factor β Receptor and Ras-MAP Kinase Pathway in Equine Sarcoid Fibroblasts
title_short Analysis of Activated Platelet-Derived Growth Factor β Receptor and Ras-MAP Kinase Pathway in Equine Sarcoid Fibroblasts
title_sort analysis of activated platelet-derived growth factor β receptor and ras-map kinase pathway in equine sarcoid fibroblasts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726019/
https://www.ncbi.nlm.nih.gov/pubmed/23936786
http://dx.doi.org/10.1155/2013/283985
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