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.

Základní údaje

Originální název

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

Autoři

ŠRÁMEK, Martin; Jakub NERADIL; Petra MACIGOVÁ; Peter MÚDRY; Kristýna POLÁŠKOVÁ; Ondřej SLABÝ; Hana NOSKOVÁ; Jaroslav ŠTĚRBA a Renata VESELSKÁ

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Kód RIV

RIV/00216224:14110/18:00106971

Organizační jednotka

Lékařská fakulta

DOI

https://doi.org/10.3390/ijms19092599

UT WoS

000449988100135

EID Scopus

2-s2.0-85052734385

Klíčová slova anglicky

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

Štítky

14110321, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 12. 3. 2019 10:06, Mgr. Pavla Foltynová, Ph.D.

Anotace

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.

Návaznosti

NV16-33209A, projekt VaV

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

NV16-34083A, projekt VaV

Název: 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 a 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, roč. 19, č. 9, s. 1-16. ISSN 1422-0067. Dostupné z: https://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 = {https://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 a 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, roč.~19, č.~9, s.~1-16. ISSN~1422-0067. Dostupné z: https://doi.org/10.3390/ijms19092599.

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