Deletion-mutant epidermal growth factor receptor in human gliomas: Effect of type II mutation on receptor function

Peter A. Humphrey*, Lisa M. Gangarosa, Albert J. Wong, Gerald E. Archer, Morten Lund-Johansen, Rolf Bjerkvig, Ole Didrik Laerum, Henry S. Friedman, Darell D. Bigner

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

86 Citations (Scopus)

Abstract

Malignant human glioma D-298 MG amplifies a rearranged epidermal growth factor receptor (EGFR) gene (c-erbB proto-oncogene), resulting in an in-frame deletion of 83 amino acids in domain IV of the extracellular domain of the EGFR. EGF and transforming growth factor-α (TGF-α) bound to the mutant EGFR with high affinity and enhanced the intrinsic mutant EGFR kinase activity. The mutant EGFR was capable of transducing EGF-stimulated glioma cell proliferation and invasiveness in an in vitro three-dimensional spheroid model. The deletion-mutant EGFR in D-298 MG is capable of being activated by growth factor; this suggests that overexpression of this mutant EGFR protein rather than structural alteration may be the more significant biologic event.

Original languageEnglish
Pages (from-to)1413-1420
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume178
Issue number3
DOIs
Publication statusPublished - 15 Aug 1991
Externally publishedYes

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