Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1783359311107325952 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6163232 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT sramekmartin effectsofsunitinibandotherkinaseinhibitorsoncellsharboringapdgfrbmutationassociatedwithinfantilemyofibromatosis AT neradiljakub effectsofsunitinibandotherkinaseinhibitorsoncellsharboringapdgfrbmutationassociatedwithinfantilemyofibromatosis AT macigovapetra effectsofsunitinibandotherkinaseinhibitorsoncellsharboringapdgfrbmutationassociatedwithinfantilemyofibromatosis AT mudrypeter effectsofsunitinibandotherkinaseinhibitorsoncellsharboringapdgfrbmutationassociatedwithinfantilemyofibromatosis AT polaskovakristyna effectsofsunitinibandotherkinaseinhibitorsoncellsharboringapdgfrbmutationassociatedwithinfantilemyofibromatosis AT slabyondrej effectsofsunitinibandotherkinaseinhibitorsoncellsharboringapdgfrbmutationassociatedwithinfantilemyofibromatosis AT noskovahana effectsofsunitinibandotherkinaseinhibitorsoncellsharboringapdgfrbmutationassociatedwithinfantilemyofibromatosis AT sterbajaroslav effectsofsunitinibandotherkinaseinhibitorsoncellsharboringapdgfrbmutationassociatedwithinfantilemyofibromatosis AT veselskarenata effectsofsunitinibandotherkinaseinhibitorsoncellsharboringapdgfrbmutationassociatedwithinfantilemyofibromatosis |