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

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Publikace nespadá pod Fakultu sportovních studií, ale pod Lékařskou fakultu. Oficiální stránka publikace je na webu muni.cz.
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ŠRÁMEK Martin NERADIL Jakub MACIGOVÁ Petra MÚDRY Peter POLÁŠKOVÁ Kristýna SLABÝ Ondřej NOSKOVÁ Hana ŠTĚRBA Jaroslav VESELSKÁ Renata

Rok publikování 2018
Druh Článek v odborném periodiku
Časopis / Zdroj International Journal of Molecular Sciences
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
www https://www.mdpi.com/1422-0067/19/9/2599
Doi http://dx.doi.org/10.3390/ijms19092599
Klíčová slova Infantile myofibromatosis; receptor tyrosine kinases; platelet-derived growth factor receptor; protein kinase inhibitors; sunitinib; erlotinib; FR180204; U0126; targeted therapy
Popis 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.
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