Amplification and expression of the epidermal growth factor receptor gene in human glioma xenografts.
Xenografts from eight malignant human gliomas were established in athymic mice and were used to study amplification and expression of the epidermal growth factor receptor (EGFR) gene. Tissue identity between biopsy and xenografts was confirmed by karyotypic profiles, which showed that each glioma xenograft retained structural abnormalities, including double minute chromosomes, present in the parent glioma. EGFR gene amplification was found in six of the eight glioma biopsies and their corresponding xenografts. Expression of the EGFR gene was measured by Scatchard analysis, affinity reactions, immunoprecipitations, Western immunoblots, and immunocytochemistry; significant expression of the EGFR gene was only detectable in xenografts with EGFR gene amplification. Moreover, five of the six xenografts with EGFR gene amplification demonstrated structural alterations of the EGFR gene, which was associated with low-molecular-weight EGFR proteins. These xenografts represent an excellent tissue source and in vivo model system for characterizing the epidermal growth factor receptor in malignant human gliomas.
Humphrey
P A
PA
Brain Tumor Research [D.D.B., M.H.W.] and Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710.
Wong
A J
AJ
Vogelstein
B
B
Friedman
H S
HS
Werner
M H
MH
Bigner
D D
DD
Bigner
S H
SH
D000818:Animals; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D005910:Glioma / Q000235:genetics*; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D007621:Karyotyping; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
D007457:Iodine Radioisotopes; D004815:Epidermal Growth Factor; D066246:ErbB Receptors