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 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.
Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Napoli, Italy.
Gennaro
G
Altamura
Annunziata
A
Corteggio
Lubna
L
Nasir
Zheng Qiang
ZQ
Yuan
Franco
F
Roperto
Giuseppe
G
Borzacchiello
D000818:Animals; D052688:Bovine papillomavirus 1 / Q000235:genetics / Q000472:pathogenicity*; D002417:Cattle; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006736:Horses / Q000378:metabolism / Q000821:virology; D020935:MAP Kinase Signaling System / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000662:veterinary / Q000821:virology
D015513:Oncogene Proteins; D020797:Receptor, Platelet-Derived Growth Factor beta