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.

Basic information

Original name

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

Authors

ŠKODA, Jan (203 Czech Republic, belonging to the institution), Jakub NERADIL (203 Czech Republic, belonging to the institution), Karel ZITTERBART (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

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

Genetics and molecular biology

Country of publisher

Greece

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 2.301

RIV identification code

RIV/00216224:14310/14:00074892

Organization unit

Faculty of Science

DOI

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

UT WoS

000330788100065

Keywords in English

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

Abstract

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.

Links

EE2.3.20.0183, research and development project

Name: Centrum experimentální biomedicíny

Citovat

ŠKODA, Jan, Jakub NERADIL, Karel ZITTERBART, Jaroslav ŠTĚRBA and 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, vol. 31, No 1, p. 480-487. ISSN 1021-335X. Available from: 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 and 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, vol.~31, No~1, p.~480-487. ISSN~1021-335X. Available from: https://dx.doi.org/10.3892/or.2013.2864.

Detailed Information on Publication Record