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c-KIT-expressing Ewing tumour cells are insensitive to imatinib mesylate (STI571).
- Source :
-
Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2002 Aug; Vol. 50 (2), pp. 167-9. Date of Electronic Publication: 2002 Jun 15. - Publication Year :
- 2002
-
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.<br />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.<br />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.<br />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.
- Subjects :
- Benzamides
Bone Neoplasms metabolism
Humans
Imatinib Mesylate
Protein-Tyrosine Kinases antagonists & inhibitors
Protein-Tyrosine Kinases biosynthesis
Reverse Transcriptase Polymerase Chain Reaction
Sarcoma, Ewing metabolism
Signal Transduction drug effects
Tumor Cells, Cultured drug effects
Tumor Cells, Cultured metabolism
Antineoplastic Agents pharmacology
Bone Neoplasms pathology
Drug Resistance, Neoplasm
Enzyme Inhibitors pharmacology
Neoplasm Proteins biosynthesis
Piperazines pharmacology
Proto-Oncogene Proteins c-kit biosynthesis
Pyrimidines pharmacology
Sarcoma, Ewing pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0344-5704
- Volume :
- 50
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cancer chemotherapy and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 12172985
- Full Text :
- https://doi.org/10.1007/s00280-002-0477-8