Molecular signalling pathways in canine gliomas

Vet Comp Oncol. 2017 Mar;15(1):133-150. doi: 10.1111/vco.12147. Epub 2015 Mar 25.

Abstract

In this study, we determined the expression of key signalling pathway proteins TP53, MDM2, P21, AKT, PTEN, RB1, P16, MTOR and MAPK in canine gliomas using western blotting. Protein expression was defined in three canine astrocytic glioma cell lines treated with CCNU, temozolamide or CPT-11 and was further evaluated in 22 spontaneous gliomas including high and low grade astrocytomas, high grade oligodendrogliomas and mixed oligoastrocytomas. Response to chemotherapeutic agents and cell survival were similar to that reported in human glioma cell lines. Alterations in expression of key human gliomagenesis pathway proteins were common in canine glioma tumour samples and segregated between oligodendroglial and astrocytic tumour types for some pathways. Both similarities and differences in protein expression were defined for canine gliomas compared to those reported in human tumour counterparts. The findings may inform more defined assessment of specific signalling pathways for targeted therapy of canine gliomas.

Keywords: astrocytoma; brain tumour; canine glioma cell lines; oligodendroglioma; signalling pathways; western blotting.

MeSH terms

  • Animals
  • Antineoplastic Agents
  • Blotting, Western / veterinary
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Brain Neoplasms / veterinary*
  • California
  • Cell Line, Tumor
  • Dog Diseases / genetics*
  • Dog Diseases / pathology
  • Dogs
  • Female
  • Genes, Tumor Suppressor
  • Glioma / genetics
  • Glioma / pathology
  • Glioma / veterinary*
  • Male
  • PTEN Phosphohydrolase / genetics
  • Proto-Oncogene Proteins c-mdm2 / genetics
  • Signal Transduction / genetics*
  • TOR Serine-Threonine Kinases / genetics
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Antineoplastic Agents
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins c-mdm2
  • TOR Serine-Threonine Kinases
  • PTEN Phosphohydrolase