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

J 2018

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

ŠRÁMEK, Martin, Jakub NERADIL, Petra MACIGOVÁ, Peter MÚDRY, Kristýna POLÁŠKOVÁ et. al.

Basic information

Original name

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

Authors

ŠRÁMEK, Martin (203 Czech Republic, belonging to the institution), Jakub NERADIL (203 Czech Republic, belonging to the institution), Petra MACIGOVÁ (203 Czech Republic, belonging to the institution), Peter MÚDRY (203 Czech Republic, belonging to the institution), Kristýna POLÁŠKOVÁ (203 Czech Republic, belonging to the institution), Ondřej SLABÝ (203 Czech Republic, belonging to the institution), Hana NOSKOVÁ (203 Czech Republic, belonging to the institution), Jaroslav ŠTĚRBA (203 Czech Republic, belonging to the institution) and Renata VESELSKÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

International Journal of Molecular Sciences, Basel, MDPI, 2018, 1422-0067

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.183

RIV identification code

RIV/00216224:14110/18:00106971

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.3390/ijms19092599

UT WoS

000449988100135

Keywords in English

Infantile myofibromatosis; receptor tyrosine kinases; platelet-derived growth factor receptor; protein kinase inhibitors; sunitinib; erlotinib; FR180204; U0126; targeted therapy

Abstract

V originále

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.

Links

NV16-33209A, research and development project

Name: Sekvenování nové generace a expresní profilování jako diagnostický podklad pro návrhy individualizovaných léčebných plánů pro děti se solidními nádory

NV16-34083A, research and development project

Name: Receptorové tyrozinkinázy a navazující signální dráhy jako potenciální cíle léčby refrakterních solidních nádorů dětského věku

Citovat

ŠRÁMEK, Martin, Jakub NERADIL, Petra MACIGOVÁ, Peter MÚDRY, Kristýna POLÁŠKOVÁ, Ondřej SLABÝ, Hana NOSKOVÁ, Jaroslav ŠTĚRBA and Renata VESELSKÁ. Effects of Sunitinib and Other Kinase Inhibitors on Cells Harboring a PDGFRB Mutation Associated with Infantile Myofibromatosis. International Journal of Molecular Sciences. Basel: MDPI, 2018, vol. 19, No 9, p. 1-16. ISSN 1422-0067. Available from: https://dx.doi.org/10.3390/ijms19092599.

@article{1498157,
   author = {Šrámek, Martin and Neradil, Jakub and Macigová, Petra and Múdry, Peter and Polášková, Kristýna and Slabý, Ondřej and Nosková, Hana and Štěrba, Jaroslav and Veselská, Renata},
   article_location = {Basel},
   article_number = {9},
   doi = {http://dx.doi.org/10.3390/ijms19092599},
   keywords = {Infantile myofibromatosis; receptor tyrosine kinases; platelet-derived growth factor receptor; protein kinase inhibitors; sunitinib; erlotinib; FR180204; U0126; targeted therapy},
   language = {eng},
   issn = {1422-0067},
   journal = {International Journal of Molecular Sciences},
   title = {Effects of Sunitinib and Other Kinase Inhibitors on Cells Harboring a PDGFRB Mutation Associated with Infantile Myofibromatosis},
   url = {https://www.mdpi.com/1422-0067/19/9/2599},
   volume = {19},
   year = {2018}
}

TY  - JOUR
ID  - 1498157
AU  - Šrámek, Martin - Neradil, Jakub - Macigová, Petra - Múdry, Peter - Polášková, Kristýna - Slabý, Ondřej - Nosková, Hana - Štěrba, Jaroslav - Veselská, Renata
PY  - 2018
TI  - Effects of Sunitinib and Other Kinase Inhibitors on Cells Harboring a PDGFRB Mutation Associated with Infantile Myofibromatosis
JF  - International Journal of Molecular Sciences
VL  - 19
IS  - 9
SP  - 1-16
EP  - 1-16
PB  - MDPI
SN  - 14220067
KW  - Infantile myofibromatosis
KW  - receptor tyrosine kinases
KW  - platelet-derived growth factor receptor
KW  - protein kinase inhibitors
KW  - sunitinib
KW  - erlotinib
KW  - FR180204
KW  - U0126
KW  - targeted therapy
UR  - https://www.mdpi.com/1422-0067/19/9/2599
L2  - https://www.mdpi.com/1422-0067/19/9/2599
N2  - 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.
ER  -

ŠRÁMEK, Martin, Jakub NERADIL, Petra MACIGOVÁ, Peter MÚDRY, Kristýna POLÁŠKOVÁ, Ondřej SLABÝ, Hana NOSKOVÁ, Jaroslav ŠTĚRBA and Renata VESELSKÁ. Effects of Sunitinib and Other Kinase Inhibitors on Cells Harboring a PDGFRB Mutation Associated with Infantile Myofibromatosis. \textit{International Journal of Molecular Sciences}. Basel: MDPI, 2018, vol.~19, No~9, p.~1-16. ISSN~1422-0067. Available from: https://dx.doi.org/10.3390/ijms19092599.

Detailed Information on Publication Record