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Title: The tumor-specific de2-7 epidermal growth factor receptor (EGFR) promotes cells survival and heterodimerizes with the wild-type EGFR.
Austin Authors: Luwor, Rodney B;Zhu, Hong-Jian;Walker, Francesca;Vitali, Angela A;Perera, Rushika M;Burgess, Antony W;Scott, Andrew M ;Johns, Terrance G
Affiliation: Tumour Targeting Program, Ludwig Institute for Cancer Research, Melbourne Branch, Austin Hospital, Heidelberg 3084, Australia
Issue Date: 12-Aug-2004
Publication information: Oncogene; 23(36): 6095-104
Abstract: Mutations of the epidermal growth factor receptor (EGFR) gene are found at a relatively high frequency in glioma, with the most common being the de2-7 EGFR (or EGFRvIII). This mutation arises from an in-frame deletion of exons 2-7, which removes 267 amino acids from the extracellular domain of the receptor. Despite being unable to bind ligand, the de2-7 EGFR is constitutively active and imparts a significant in vivo growth advantage to glioma cells. In order to examine the signalling pathways activated by the de2-7 EGFR and its biological effects in an in vitro system, the de2-7 EGFR gene was transfected into the murine IL-3-dependent pro-B-cell line BaF/3. Expression of the de2-7 EGFR enhanced the survival of BaF/3 cells in the absence of IL-3 by reducing apoptosis in a phosphatidylinositol 3-kinase (PI3-K)-dependent manner. Interestingly, while de2-7 EGFR also enhanced proliferation of BaF/3 cells in low levels of IL-3, this effect was independent of PI3-K. Survival and proliferation were further enhanced when BaF/3 cells were cotransfected with the de2-7 and wt EGFR. This was due to heterodimerization between the de2-7 and wt EGFR leading to trans-phosphorylation of the wt EGFR. This observation is directly relevant to glioma where de2-7 and wt EGFR appear to be coexpressed. Thus, expression of de2-7 EGFR in BaF/3 cells provides an in vitro model for evaluating the signalling pathways activated by this receptor.
Gov't Doc #: 15221011
DOI: 10.1038/sj.onc.1207870
Type: Journal Article
Subjects: Animals
Cell Cycle
Cell Division
Cell Line
Cell Survival
Genes, erbB
Receptor, Epidermal Growth Factor.genetics.metabolism
Sequence Deletion
Signal Transduction
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