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 (203 Česká republika, domácí), Jakub NERADIL (203 Česká republika, domácí), Petra MACIGOVÁ (203 Česká republika, domácí), Peter MÚDRY (203 Česká republika, domácí), Kristýna POLÁŠKOVÁ (203 Česká republika, domácí), Ondřej SLABÝ (203 Česká republika, domácí), Hana NOSKOVÁ (203 Česká republika, domácí), Jaroslav ŠTĚRBA (203 Česká republika, domácí) a Renata VESELSKÁ (203 Česká republika, garant, domácí)

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

Impakt faktor

Impact factor: 4.183

Kód RIV

RIV/00216224:14110/18:00106971

Organizační jednotka

Lékařská fakulta

DOI

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

UT WoS

000449988100135

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

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