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Departments of Pathology [S. H. B., P. A. H., H. S. F., D. D. B.] and Pediatrics [H. S. F.] and Preuss Laboratory for Brain Tumor Research [D. D. B.], Duke University Medical Center, Durham, North Carolina 27710; Fox Chase Oncology Center, Philadelphia, Pennsylvania 19111 [A. J. W.]; Department of Oncology, Johns Hopkins Medical Center, Baltimore, Maryland 21205 [B. V.]; and Department of Pathology, Central Hospital, Skövde, Sweden [J. M.]
Both permanent cultured cell lines and athymic mouse xenografts were established from two human glioblastomas. Biopsies from D-245 MG and D-270 MG contained amplified and rearranged epidermal growth factor receptor (EGFR) genes. Although the gene amplification and rearrangement seen originally was maintained in the xenografts, cultured cell lines established from these biopsies lost the amplified rearranged genes in vitro. Analysis of these cell lines and 11 additional permanent human glioma cell lines with normal EGFR gene copy number showed from 2.7 x 103 to 4.1 x 105 high affinity EGFRs/cell by radioreceptor assay. The RNase A protection assay showed minimal differences in the quantity of EGFR mRNA among the 13 glioma lines, while the D-245 MG and D-270 MG xenografts expressed approximately 10–20 times as much EGFR mRNA as the corresponding cell lines. Immunoprecipitation of EGFR from these lines, including D-245 MG and D-270 MG, demonstrated only the intact Mr 170,000 Da form, while truncated Mr 145,000 Da and 100,000 Da EGFR proteins were immunoprecipitated from the D-270 MG and D-245 MG xenografts, respectively. These studies demonstrate that gliomas with amplification of the EGFR gene are capable of establishing in culture but that the amplified rearranged genes are not maintained. Possible explanations are that the abnormal genes are lost during serial passage or that the cells with amplified rearranged genes only represent a minor subpopulation of cells, which are unable to grow in culture. In either case, these observations suggest that high expression and structural abnormalities of EGFR proteins generated by amplification and rearrangement of the EGFR gene provide a growth advantage for gliomas in vivo but not in vitro.
1 This investigation was supported in part by Grants CA-11898 (D. D. B), CA-43460 (B. V.), CA-44640 (H. S. F.), and CA-43722 (S. H. B.) from the National Cancer Institute, Grant P01-NS-20023 (D. D. B., H. S. F., P. A. H., S. H. B.) from NINCDS, and the Swedish Cancer Society (J. M.).
2 To whom requests for reprints should be addressed.
Received 6/21/90. Accepted 9/14/90.
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