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Amplification and Expression of the Epidermal Growth Factor Receptor Gene in Human Glioma Xenografts¹

Preuss Laboratory for Brain Tumor Research [D. D. B., M. H. W.] and Departments of Pathology [P. A. H., S. H. B., H. S. F., D. D. B.], Surgery [D. D. B.], and Pediatrics [H. S. F.], Duke University Medical Center, Durham, North Carolina 27710, and the Department of Oncology [A. J. W., B. V.], The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

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.

¹ Supported by Grants CA-11898, NS-20023, CA-43722, CA-43460, CA-09243, and 5 T32 AI 07240 and by the Association for Brain Tumor Research (P. A. H., M. H. W.).

² To whom requests for reprints should be addressed.

Received 7/ 3/87. Revised 12/28/87. Accepted 1/18/88.

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