Expression of cytoplasmic-domain substituted epidermal growth factor receptor inhibits tumorigenicity of EGFR-overexpressed human glioblastoma multiforme

  • Authors:
    • Ko-Jiunn Liu
    • Chun-Ting Chen
    • Wensi S. Hu
    • Yi-Mei Hung
    • Chiung-Yueh Hsu
    • Bin-Fay Chuang
    • Shin-Hun Juang
  • View Affiliations

  • Published online on: March 1, 2004     https://doi.org/10.3892/ijo.24.3.581
  • Pages: 581-590
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Abstract

The accumulated results of recent clinical studies have indicated that aberrant epidermal growth factor receptor (EGFR) activation due to gene amplification and/or rearrangement contributes to increased malignancy and poor prognosis in many human cancers, especially in human glioblastoma multiforme (GBM). The elevated EGFR signaling in GBM has been correlated with shorter interval to relapse and lower survival rates, even in patients treated with surgery, radiation therapy, and/or chemotherapy. Therefore, the blockade of EGFR signaling in GBM may provide an ideal alternative therapeutic strategy. In this study, two EGFR-overexpressing human GBM cell lines (i.e., DBTRG and GBM 8901) were used as a model system. We demonstrated that expression of a human EGFR (EGFRt-EGFP) chimera protein in which the cytoplasmic domain is substituted by EGFP significantly reduced the EGF-induced endogenous EGFR autophosphorylation, EGF-induced downstream extra-cellular signal-regulated kinase (ERK) and Akt signaling, and the proportion of internalized receptors in EGF stimulated cells. Furthermore, these cells' anchorage-independent growth in vitro was decreased and their tumorigenicity in vivo abrogated or strongly suppressed. Our data suggest that EGFRt-EGFP abrogates tumor growth by disrupting receptor activation via competing for EGF-like ligands, forming non-activated heterodimers with endogenous EGFR, and inhibiting the EGFR endosomal signaling by substantially diminishing receptor internalization. This treatment modality (termed ‘dominant-negative EGFR therapy’) and its efficacy for gliomas or other tumors are under scrutiny.

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March 2004
Volume 24 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Liu, K., Chen, C., Hu, W.S., Hung, Y., Hsu, C., Chuang, B., & Juang, S. (2004). Expression of cytoplasmic-domain substituted epidermal growth factor receptor inhibits tumorigenicity of EGFR-overexpressed human glioblastoma multiforme. International Journal of Oncology, 24, 581-590. https://doi.org/10.3892/ijo.24.3.581
MLA
Liu, K., Chen, C., Hu, W. S., Hung, Y., Hsu, C., Chuang, B., Juang, S."Expression of cytoplasmic-domain substituted epidermal growth factor receptor inhibits tumorigenicity of EGFR-overexpressed human glioblastoma multiforme". International Journal of Oncology 24.3 (2004): 581-590.
Chicago
Liu, K., Chen, C., Hu, W. S., Hung, Y., Hsu, C., Chuang, B., Juang, S."Expression of cytoplasmic-domain substituted epidermal growth factor receptor inhibits tumorigenicity of EGFR-overexpressed human glioblastoma multiforme". International Journal of Oncology 24, no. 3 (2004): 581-590. https://doi.org/10.3892/ijo.24.3.581