Expression and activation of platelet-derived growth factor β receptor, mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) and extracellular signal-regulated kinase (ERK) in canine mammary tumours

Res Vet Sci. 2017 Feb;110:29-33. doi: 10.1016/j.rvsc.2016.10.014. Epub 2016 Oct 28.

Abstract

Canine mammary tumours are frequent neoplasms mostly affecting intact female dogs, for which no 100% efficient therapy is available. Platelet derived growth factor β receptor (PDGFβR) is a tyrosine kinase receptor (TKR) with a potential role in human breast cancer and a series of canine tumours. In this study we demonstrated, for the first time, expression of PDGFβR and its downstream transduction molecules, mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) and extracellular signal-regulated kinase (ERK), as well as their activated forms in canine mammary tumours by both biochemical analysis and immunohistochemistry. PDGFβR was expressed and hyperphosphorylated in the majority of tumour samples and tumour derived cell lines. Additionally, both MEK and ERK were expressed and activated in cell lines as well as biopsies. TKR inhibitors (TKRi) are currently under investigation as possible therapy in human breast and several canine tumours, thus our in vivo and in vitro findings pave the way for future studies aimed at establishing a potential therapeutic employment of TKRi for the treatment of canine mammary cancer.

Keywords: ERK; MEK; Oncology; PDGFβR; TKR inhibitors.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Dog Diseases / genetics*
  • Dog Diseases / metabolism
  • Dogs
  • Extracellular Signal-Regulated MAP Kinases / genetics*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Mammary Neoplasms, Animal / genetics*
  • Mammary Neoplasms, Animal / metabolism
  • Mitogen-Activated Protein Kinases / genetics*
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphorylation
  • Receptor, Platelet-Derived Growth Factor beta / genetics*
  • Receptor, Platelet-Derived Growth Factor beta / metabolism
  • Signal Transduction

Substances

  • Receptor, Platelet-Derived Growth Factor beta
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinases