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

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 hav...

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Autores principales: Sramek, Martin, Neradil, Jakub, Macigova, Petra, Mudry, Peter, Polaskova, Kristyna, Slaby, Ondrej, Noskova, Hana, Sterba, Jaroslav, Veselska, Renata
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163232/
https://www.ncbi.nlm.nih.gov/pubmed/30200486
http://dx.doi.org/10.3390/ijms19092599
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author Sramek, Martin
Neradil, Jakub
Macigova, Petra
Mudry, Peter
Polaskova, Kristyna
Slaby, Ondrej
Noskova, Hana
Sterba, Jaroslav
Veselska, Renata
author_facet Sramek, Martin
Neradil, Jakub
Macigova, Petra
Mudry, Peter
Polaskova, Kristyna
Slaby, Ondrej
Noskova, Hana
Sterba, Jaroslav
Veselska, Renata
author_sort Sramek, Martin
collection PubMed
description 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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spelling pubmed-61632322018-10-10 Effects of Sunitinib and Other Kinase Inhibitors on Cells Harboring a PDGFRB Mutation Associated with Infantile Myofibromatosis Sramek, Martin Neradil, Jakub Macigova, Petra Mudry, Peter Polaskova, Kristyna Slaby, Ondrej Noskova, Hana Sterba, Jaroslav Veselska, Renata Int J Mol Sci Article 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. MDPI 2018-09-01 /pmc/articles/PMC6163232/ /pubmed/30200486 http://dx.doi.org/10.3390/ijms19092599 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sramek, Martin
Neradil, Jakub
Macigova, Petra
Mudry, Peter
Polaskova, Kristyna
Slaby, Ondrej
Noskova, Hana
Sterba, Jaroslav
Veselska, Renata
Effects of Sunitinib and Other Kinase Inhibitors on Cells Harboring a PDGFRB Mutation Associated with Infantile Myofibromatosis
title Effects of Sunitinib and Other Kinase Inhibitors on Cells Harboring a PDGFRB Mutation Associated with Infantile Myofibromatosis
title_full Effects of Sunitinib and Other Kinase Inhibitors on Cells Harboring a PDGFRB Mutation Associated with Infantile Myofibromatosis
title_fullStr Effects of Sunitinib and Other Kinase Inhibitors on Cells Harboring a PDGFRB Mutation Associated with Infantile Myofibromatosis
title_full_unstemmed Effects of Sunitinib and Other Kinase Inhibitors on Cells Harboring a PDGFRB Mutation Associated with Infantile Myofibromatosis
title_short Effects of Sunitinib and Other Kinase Inhibitors on Cells Harboring a PDGFRB Mutation Associated with Infantile Myofibromatosis
title_sort effects of sunitinib and other kinase inhibitors on cells harboring a pdgfrb mutation associated with infantile myofibromatosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163232/
https://www.ncbi.nlm.nih.gov/pubmed/30200486
http://dx.doi.org/10.3390/ijms19092599
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