EGFR signaling in the HGG-02 glioblastoma cell line with an
unusual loss of EGFR gene copy

J 2014

EGFR signaling in the HGG-02 glioblastoma cell line with an unusual loss of EGFR gene copy

ŠKODA, Jan, Jakub NERADIL, Karel ZITTERBART, Jaroslav ŠTĚRBA, Renata VESELSKÁ et. al.

Základní údaje

Originální název

EGFR signaling in the HGG-02 glioblastoma cell line with an unusual loss of EGFR gene copy

Autoři

ŠKODA, Jan (203 Česká republika, domácí), Jakub NERADIL (203 Česká republika, domácí), Karel ZITTERBART (203 Česká republika, domácí), Jaroslav ŠTĚRBA (203 Česká republika, domácí) a Renata VESELSKÁ (203 Česká republika, garant, domácí)

Vydání

Oncology Reports, Athens, Spandidos Publications Ltd, 2014, 1021-335X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

Genetika a molekulární biologie

Stát vydavatele

Řecko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.301

Kód RIV

RIV/00216224:14310/14:00074892

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.3892/or.2013.2864

UT WoS

000330788100065

Klíčová slova anglicky

glioblastoma multiforme; epidermal growth factor receptor signaling; PDGFR; TAM receptors; receptor tyrosine kinase; mitogen-activated protein kinase

Štítky

AKR, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 25. 11. 2015 22:06, prof. RNDr. Renata Veselská, Ph.D., M.Sc.

Anotace

V originále

Epidermal growth factor receptor (EGFR) gene amplification and the overexpression of EGFR are described as common features of glioblastoma multiforme (GBM). Nevertheless, we previously reported the loss of EGFR gene copy in a GBM specimen from a patient with an unusually favorable course of the disease, and the HGG-02 cell line with this aberration was successfully derived from this tumor. Here, we present a detailed analysis of changes in gene expression and cell signaling in the HGG-02 cell line; the GM7 reference cell line with a standard EGFR gene copy number derived from a very aggressive GBM was used as a control. We confirmed the downregulation of EGFR expression and signaling in HGG-02 cells using different methods (RTK analysis, gene profiling and RT-PCR). Other changes that may have contributed to the non-aggressive phenotype of the primary tumor were identified, including the downregulated phosphorylation of the Axl and Trk receptors, as well as increased activity of JNK and p38 kinases. Notably, differences in PDGF signaling were detected in both of these cell lines; HGG-02 cells preferentially expressed and signaled through PDGFRalpha, and PDGFRbeta was strongly overexpressed and phosphorylated in the GM7 reference cell line. Using expression profiling of cancer-related genes, we revealed the specific profile of HGG-02 cells that included upregulated tumor-suppressors as well as downregulated genes associated with the extracellular matrix. This study represents the first comprehensive analysis of gene expression and cell signaling in glioblastoma cells with lower EGFR gene dosage. As indicated by our results, the TAM receptors, Trk receptors and PDGFRs need to be investigated further since their regulation appears to be important for glioblastoma biological features as well as the clinical course of the disease.

Návaznosti

EE2.3.20.0183, projekt VaV

Název: Centrum experimentální biomedicíny

Citovat

ŠKODA, Jan, Jakub NERADIL, Karel ZITTERBART, Jaroslav ŠTĚRBA a Renata VESELSKÁ. EGFR signaling in the HGG-02 glioblastoma cell line with an unusual loss of EGFR gene copy. Oncology Reports. Athens: Spandidos Publications Ltd, 2014, roč. 31, č. 1, s. 480-487. ISSN 1021-335X. Dostupné z: https://dx.doi.org/10.3892/or.2013.2864.

@article{1159058,
   author = {Škoda, Jan and Neradil, Jakub and Zitterbart, Karel and Štěrba, Jaroslav and Veselská, Renata},
   article_location = {Athens},
   article_number = {1},
   doi = {http://dx.doi.org/10.3892/or.2013.2864},
   keywords = {glioblastoma multiforme; epidermal growth factor receptor signaling; PDGFR; TAM receptors; receptor tyrosine kinase; mitogen-activated protein kinase},
   language = {eng},
   issn = {1021-335X},
   journal = {Oncology Reports},
   title = {EGFR signaling in the HGG-02 glioblastoma cell line with an unusual loss of EGFR gene copy},
   url = {http://www.spandidos-publications.com/or/31/1/480},
   volume = {31},
   year = {2014}
}

TY  - JOUR
ID  - 1159058
AU  - Škoda, Jan - Neradil, Jakub - Zitterbart, Karel - Štěrba, Jaroslav - Veselská, Renata
PY  - 2014
TI  - EGFR signaling in the HGG-02 glioblastoma cell line with an unusual loss of EGFR gene copy
JF  - Oncology Reports
VL  - 31
IS  - 1
SP  - 480-487
EP  - 480-487
PB  - Spandidos Publications Ltd
SN  - 1021335X
KW  - glioblastoma multiforme
KW  - epidermal growth factor receptor signaling
KW  - PDGFR
KW  - TAM receptors
KW  - receptor tyrosine kinase
KW  - mitogen-activated protein kinase
UR  - http://www.spandidos-publications.com/or/31/1/480
L2  - http://www.spandidos-publications.com/or/31/1/480
N2  - Epidermal growth factor receptor (EGFR) gene amplification and the overexpression of EGFR are described as common features of glioblastoma multiforme (GBM). Nevertheless, we previously reported the loss of EGFR gene copy in a GBM specimen from a patient with an unusually favorable course of the disease, and the HGG-02 cell line with this aberration was successfully derived from this tumor. Here, we present a detailed analysis of changes in gene expression and cell signaling in the HGG-02 cell line; the GM7 reference cell line with a standard EGFR gene copy number derived from a very aggressive GBM was used as a control. We confirmed the downregulation of EGFR expression and signaling in HGG-02 cells using different methods (RTK analysis, gene profiling and RT-PCR). Other changes that may have contributed to the non-aggressive phenotype of the primary tumor were identified, including the downregulated phosphorylation of the Axl and Trk receptors, as well as increased activity of JNK and p38 kinases. Notably, differences in PDGF signaling were detected in both of these cell lines; HGG-02 cells preferentially expressed and signaled through PDGFRalpha, and PDGFRbeta was strongly overexpressed and phosphorylated in the GM7 reference cell line. Using expression profiling of cancer-related genes, we revealed the specific profile of HGG-02 cells that included upregulated tumor-suppressors as well as downregulated genes associated with the extracellular matrix. This study represents the first comprehensive analysis of gene expression and cell signaling in glioblastoma cells with lower EGFR gene dosage. As indicated by our results, the TAM receptors, Trk receptors and PDGFRs need to be investigated further since their regulation appears to be important for glioblastoma biological features as well as the clinical course of the disease.
ER  -

ŠKODA, Jan, Jakub NERADIL, Karel ZITTERBART, Jaroslav ŠTĚRBA a Renata VESELSKÁ. EGFR signaling in the HGG-02 glioblastoma cell line with an unusual loss of EGFR gene copy. \textit{Oncology Reports}. Athens: Spandidos Publications Ltd, 2014, roč.~31, č.~1, s.~480-487. ISSN~1021-335X. Dostupné z: https://dx.doi.org/10.3892/or.2013.2864.

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