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BioMed research international2013; 2013; 283985; doi: 10.1155/2013/283985

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

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.
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Publication Date: 2013-07-11 PubMed ID: 23936786PubMed Central: PMC3726019DOI: 10.1155/2013/283985Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research studied the biochemical pathways, specifically Ras-MAP kinase pathway, involved in equine sarcoids, a type of skin tumour in horses, and the impacts of the cancer treatment drug imatinib on the disease.

Background

  • Equine sarcoids are skin tumours, typically found in horses, that originate from fibroblast cells.
  • The primary cause of this disease is identified to be Bovine papillomavirus type-1 (BPV-1), with BPV-2 being less common.
  • The transforming activity of BPV involves an important protein, E5, which binds to a receptor known as the platelet-derived growth factor β receptor (PDGFβR), triggering its activation.

Research Findings

  • The researchers used coimmunoprecipitation and immunoblotting techniques to show that in cell lines derived from equine sarcoid, PDGFβR is activated and connected with molecules related to the Ras-mitogen-activated protein kinase-ERK pathway. This then results in the enhancement of the Ras pathway.
  • Imatinib mesylate, a drug used for treating various forms of cancer in humans and animals, was found to inhibit the activation of the PDGFβR. It acts as a tyrosine kinase receptors inhibitor, selectively halting this receptor’s activation.
  • Through cell viability assays, the team demonstrated that treatment with imatinib reduced the viability of sarcoid fibroblasts in a dose-dependent manner, indicating its effective antitumor activity.

Implications

  • These findings contribute to the broader understanding of the molecular mechanisms that underlie the pathology of equine sarcoids.
  • The research also suggests a promising therapeutic approach using imatinib for treating this common equine skin tumour.

Cite This Article

APA
Altamura G, Corteggio A, Nasir L, Yuan ZQ, Roperto F, Borzacchiello G. (2013). Analysis of activated platelet-derived growth factor β receptor and Ras-MAP kinase pathway in equine sarcoid fibroblasts. Biomed Res Int, 2013, 283985. https://doi.org/10.1155/2013/283985

Publication

BioMed research international
ISSN: 2314-6141
NlmUniqueID: 101600173
Country: United States
Language: English
Volume: 2013
Pages: 283985
PII: 283985

Researcher Affiliations

Altamura, Gennaro
  • Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Napoli, Italy.
Corteggio, Annunziata
    Nasir, Lubna
      Yuan, Zheng Qiang
        Roperto, Franco
          Borzacchiello, Giuseppe

            MeSH Terms

            • Animals
            • Bovine papillomavirus 1 / genetics
            • Bovine papillomavirus 1 / pathogenicity
            • Cattle
            • Fibroblasts / metabolism
            • Fibroblasts / pathology
            • Horses / metabolism
            • Horses / virology
            • MAP Kinase Signaling System / genetics
            • Oncogene Proteins / genetics
            • Oncogene Proteins / metabolism
            • Phosphorylation
            • Receptor, Platelet-Derived Growth Factor beta / genetics
            • Receptor, Platelet-Derived Growth Factor beta / metabolism
            • Skin Neoplasms / metabolism
            • Skin Neoplasms / pathology
            • Skin Neoplasms / veterinary
            • Skin Neoplasms / virology

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            Citations

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