Deletion-mutant epidermal growth factor receptor in human gliomas: effects of type II mutation on receptor function.
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-a (TGF-a) 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.
Departments of Pathology, Duke University Medical Center, Durham, NC 27710.
P A
PA
Humphrey
L M
LM
Gangarosa
A J
AJ
Wong
G E
GE
Archer
M
M
Lund-Johansen
R
R
Bjerkvig
O D
OD
Laerum
H S
HS
Friedman
D D
DD
Bigner
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D002872:Chromosome Deletion; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005784:Gene Amplification; D015321:Gene Rearrangement; D005910:Glioma / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha / Q000378:metabolism / Q000494:pharmacology*
D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha; C000715470:MAS1 protein, human