c-KIT-expressing Ewing tumour cells are insensitive to imatinib mesylate (STI571)

Cancer Chemother Pharmacol. 2002 Aug;50(2):167-9. doi: 10.1007/s00280-002-0477-8. Epub 2002 Jun 15.

Abstract

Purpose: In order to determine whether Ewing tumour patients may be potential candidates for imatinib mesylate therapy, we analysed the expression of the currently known imatinib mesylate-sensitive tyrosine kinases and tested sensitivity to imatinib mesylate in a panel of eight Ewing tumour cell lines in vitro.

Methods: Expression of the different tyrosine kinases was assessed by flow cytometry and RT-PCR. Sensitivity to imatinib mesylate was analysed using a standard MTT proliferation assay.

Results: Flow cytometric and RT-PCR analyses in a panel of eight Ewing tumour cell lines demonstrated expression of several imatinib mesylate-sensitive tyrosine kinases, including c-KIT, platelet-derived growth factor receptor, c-ABL and c-ARG. However, in the MTT proliferation assay, all eight Ewing tumour cell lines were found to be resistant to imatinib mesylate at concentrations ranging from 0.1 to 10 micro M.

Conclusions: Despite the expression of imatinib mesylate-sensitive tyrosine kinases, Ewing tumour cells proved resistant to imatinib mesylate in vitro. This observation has implications for the selection of patients for experimental therapy with imatinib mesylate.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Benzamides
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology*
  • Drug Resistance, Neoplasm*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Imatinib Mesylate
  • Neoplasm Proteins / biosynthesis*
  • Piperazines / pharmacology*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / biosynthesis
  • Proto-Oncogene Proteins c-kit / biosynthesis*
  • Pyrimidines / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sarcoma, Ewing / metabolism
  • Sarcoma, Ewing / pathology*
  • Signal Transduction / drug effects
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism

Substances

  • Antineoplastic Agents
  • Benzamides
  • Enzyme Inhibitors
  • Neoplasm Proteins
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-kit