Effects of Sunitinib and Other Kinase Inhibitors on Cells Harboring a PDGFRB Mutation Associated with Infantile Myofibromatosis.

Autor: Sramek M; Laboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, 61137 Brno, Czech Republic. martin.sramek@mail.muni.cz.; Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, 66263 Brno, Czech Republic. martin.sramek@mail.muni.cz.; International Clinical Research Center, St. Anne's University Hospital, 65691 Brno, Czech Republic. martin.sramek@mail.muni.cz., Neradil J; Laboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, 61137 Brno, Czech Republic. jneradil@sci.muni.cz.; Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, 66263 Brno, Czech Republic. jneradil@sci.muni.cz.; International Clinical Research Center, St. Anne's University Hospital, 65691 Brno, Czech Republic. jneradil@sci.muni.cz., Macigova P; Laboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, 61137 Brno, Czech Republic. macigova@med.muni.cz.; Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, 66263 Brno, Czech Republic. macigova@med.muni.cz., Mudry P; Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, 66263 Brno, Czech Republic. mudry.peter@fnbrno.cz., Polaskova K; Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, 66263 Brno, Czech Republic. polaskova.kristyna@fnbrno.cz.; International Clinical Research Center, St. Anne's University Hospital, 65691 Brno, Czech Republic. polaskova.kristyna@fnbrno.cz., Slaby O; Central European Institute of Technology, Masaryk University, 62500 Brno, Czech Republic. ondrej.slaby@ceitec.muni.cz., Noskova H; Central European Institute of Technology, Masaryk University, 62500 Brno, Czech Republic. hana.noskova@ceitec.muni.cz., Sterba J; Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, 66263 Brno, Czech Republic. sterba.jaroslav@fnbrno.cz.; International Clinical Research Center, St. Anne's University Hospital, 65691 Brno, Czech Republic. sterba.jaroslav@fnbrno.cz., Veselska R; Laboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, 61137 Brno, Czech Republic. veselska@sci.muni.cz.; Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, 66263 Brno, Czech Republic. veselska@sci.muni.cz.; International Clinical Research Center, St. Anne's University Hospital, 65691 Brno, Czech Republic. veselska@sci.muni.cz.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2018 Sep 01; Vol. 19 (9). Date of Electronic Publication: 2018 Sep 01.
DOI: 10.3390/ijms19092599
Abstrakt: Infantile myofibromatosis represents one of the most common proliferative fibrous tumors of infancy and childhood. More effective treatment is needed for drug-resistant patients, and targeted therapy using specific protein kinase inhibitors could be a promising strategy. To date, several studies have confirmed a connection between the p.R561C mutation in gene encoding platelet-derived growth factor receptor beta (PDGFR-beta) and the development of infantile myofibromatosis. This study aimed to analyze the phosphorylation of important kinases in the NSTS-47 cell line derived from a tumor of a boy with infantile myofibromatosis who harbored the p.R561C mutation in PDGFR-beta. The second aim of this study was to investigate the effects of selected protein kinase inhibitors on cell signaling and the proliferative activity of NSTS-47 cells. We confirmed that this tumor cell line showed very high phosphorylation levels of PDGFR-beta, extracellular signal-regulated kinases (ERK) 1/2 and several other protein kinases. We also observed that PDGFR-beta phosphorylation in tumor cells is reduced by the receptor tyrosine kinase inhibitor sunitinib. In contrast, MAPK/ERK kinases (MEK) 1/2 and ERK1/2 kinases remained constitutively phosphorylated after treatment with sunitinib and other relevant protein kinase inhibitors. Our study showed that sunitinib is a very promising agent that affects the proliferation of tumor cells with a p.R561C mutation in PDGFR-beta.
Databáze: MEDLINE
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