Gross, Dietmar and Bernhardt, Günther and Buschauer, Armin (2006) Platelet-derived growth factor receptor independent proliferation of human glioblastoma cells: selective tyrosine kinase inhibitors lack antiproliferative activity. Journal of Cancer Research and Clinical Oncology 132 (9), pp. 589-599.
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PURPOSE: The aim of this study was to investigate the role of platelet-derived growth factor (PDGF) and PDGF receptors (PDGFRs) in the proliferation of human glioblastoma cells as a prerequisite for a new therapeutic approach to the treatment of malignant brain tumors with selective tyrosine kinase inhibitors such as imatinib. METHODS AND RESULTS: In the human glioblastoma cell lines U-87 MG, U-118 MG and U-373 MG different PDGF and PDGFR mRNAs were detected by RT-PCR, and the expression of the receptor proteins was demonstrated by immunostaining and flow cytometry. Moreover, functional activity of PDGFRs was demonstrated in PDGFRbeta expressing glioblastoma cell variants by measuring the mobilization of intracellular Ca(2+) upon PDGF-BB stimulation. However, addition of PDGF-BB to the serum-free culture medium had no stimulatory effect on cell proliferation. Furthermore, cell growth in serum-supplemented and serum-free medium was not affected by imatinib, leflunomide and AG-1296 at therapeutically relevant concentrations. CONCLUSION: Our results suggest that clinical antitumor effects of imatinib on glioblastoma, if any, are not mediated by the PDGFR.
|Institutions:||Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer)|
|Keywords:||Platelet-derived growth factor receptor - Human glioblastoma cells - Imatinib|
|Subjects:||500 Science > 570 Life sciences|
600 Technology > 610 Medical sciences Medicine
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Yes|
|Owner:||Prof. Armin Buschauer|
|Deposited On:||21 Feb 2008 08:37|
|Last Modified:||05 Aug 2009 13:42|