國家衛生研究院 NHRI:Item 3990099045/2752

NHRI > National Institute of Cancer Research > Shin-Hun P. Juang(1997-2004) > Periodical Articles > Item 3990099045/2752

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/2752

Title:	Expression of cytoplasmic-domain substituted epidermal growth factor receptor inhibits tumorigenicity of EGFR-overexpressed human glioblastoma multiforme
Authors:	Liu, KJ;Chen, CT;Hu, WS;Hung, YM;Hsu, CY;Chuang, BF;Juang, SH
Contributors:	National Institute of Cancer Research
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 (EGFR(t)-EGFP) chimera protein in which the cytoplasmic domain is substituted by EGFP significantly reduced the EGF-induced endogenous EGFR autophosphorylation, EGF-induced downstream extracellular 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 EGFR(t)-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.
Keywords:	Oncology
Date:	2004-03
Relation:	International Journal of Oncology. 2004 Mar;24(3):581-590.
Link to:	http://www.ncbi.nlm.nih.gov/sites/entrez?myncbishare=nhrilib&Db=pubmed&Cmd=DetailsSearch&Term=14767543
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1019-6439&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000188956800014
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=6044226729
Appears in Collections:	[Shin-Hun P. Juang(1997-2004)] Periodical Articles [Ko-Jiunn Liu] Periodical Articles

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