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The tumor-specific de2–7 epidermal growth factor receptor (EGFR) promotes cells survival and heterodimerizes with the wild-type EGFR

Oncogene volume 23, pages 6095–6104 (2004)Cite this article

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.

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Acknowledgements

This work was supported by the NH&MRC of Australia.

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Authors and Affiliations

  1. Tumour Targeting Program, Ludwig Institute for Cancer Research, Melbourne Branch, Austin Hospital, Heidelberg, 3084, Australia

    Rodney B Luwor, Angela A Vitali, Rushika M Perera, Andrew M Scott & Terrance G Johns

  2. Epithelial Biochemistry Laboratory, Royal Melbourne Hospital, Parkville, 3050, Australia

    Hong-Jian Zhu, Francesca Walker & Antony W Burgess

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  1. Rodney B Luwor
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  2. Hong-Jian Zhu
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Correspondence to Terrance G Johns.

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Luwor, R., Zhu, HJ., Walker, F. et al. The tumor-specific de2–7 epidermal growth factor receptor (EGFR) promotes cells survival and heterodimerizes with the wild-type EGFR. Oncogene 23, 6095–6104 (2004). https://doi.org/10.1038/sj.onc.1207870

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