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

  • Authors:
    • Jan Skoda
    • Jakub Neradil
    • Karel Zitterbart
    • Jaroslav Sterba
    • Renata Veselska

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  • Published online on: November 20, 2013     https://doi.org/10.3892/or.2013.2864
  • Pages: 480-487
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Abstract

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 PDGFRα, and PDGFRβ 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.
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2014-January
Volume 31 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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  • Impact Factor: 3.8
  • Ranked Oncology
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  • CiteScore: 8.5
  • CiteScore Rank: Q1: #74/404 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.719
  • SCImago Journal Rank (SJR): 0.864
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Spandidos Publications style
Skoda J, Neradil J, Zitterbart K, Sterba J and Veselska R: EGFR signaling in the HGG-02 glioblastoma cell line with an unusual loss of EGFR gene copy. Oncol Rep 31: 480-487, 2014.
APA
Skoda, J., Neradil, J., Zitterbart, K., Sterba, J., & Veselska, R. (2014). EGFR signaling in the HGG-02 glioblastoma cell line with an unusual loss of EGFR gene copy. Oncology Reports, 31, 480-487. https://doi.org/10.3892/or.2013.2864
MLA
Skoda, J., Neradil, J., Zitterbart, K., Sterba, J., Veselska, R."EGFR signaling in the HGG-02 glioblastoma cell line with an unusual loss of EGFR gene copy". Oncology Reports 31.1 (2014): 480-487.
Chicago
Skoda, J., Neradil, J., Zitterbart, K., Sterba, J., Veselska, R."EGFR signaling in the HGG-02 glioblastoma cell line with an unusual loss of EGFR gene copy". Oncology Reports 31, no. 1 (2014): 480-487. https://doi.org/10.3892/or.2013.2864