Analysis of activated platelet-derived growth factor β receptor and Ras-MAP kinase pathway in equine sarcoid fibroblasts

Altamura, G., Corteggio, A., Nasir, L., Yuan, Z., Roperto, F. and Borzacchiello, G. (2013) Analysis of activated platelet-derived growth factor β receptor and Ras-MAP kinase pathway in equine sarcoid fibroblasts. BioMed Research International, 2013(283985), (doi: 10.1155/2013/283985)

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Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Nasir, Professor Lubna and Yuan, Dr Zhengqiang
Authors: Altamura, G., Corteggio, A., Nasir, L., Yuan, Z., Roperto, F., and Borzacchiello, G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:BioMed Research International
Publisher:Hindawi Publishing Corporation
ISSN:2314-6133
ISSN (Online):2314-6141
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in BioMed Research International 2013(283985)
Publisher Policy:Reproduced under a Creative Commons License

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