c-KIT-expressing Ewing tumour cells are insensitive to imatinib mesylate (STI571).
OBJECTIVE
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.
Hotfilder
Marc
M
University Children's Hospital Muenster, Department of Pediatric Hematology and Oncology, University of Muenster, Albert-Schweitzer-Str. 33, 48129 Muenster, Germany.
Lanvers
Claudia
C
Jürgens
Heribert
H
Boos
Joachim
J
Vormoor
Josef
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D000068877:Imatinib Mesylate; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010879:Piperazines / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D011743:Pyrimidines / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012512:Sarcoma, Ewing / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit