Characterization of the epidermal growth factor receptor in human glioma cell lines and xenografts

Sandra H. Bigner, Peter A. Humphrey, Albert J. Wong, Bert Vogelstein, Joachim Mark, Henry S. Friedman, Bert Vogelstein

Research output: Contribution to journalArticle

Abstract

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 × 103 to 4.1 × 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 mach 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 ire 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.

Original languageEnglish (US)
Pages (from-to)8017-8022
Number of pages6
JournalCancer Research
Volume50
Issue number24
StatePublished - Dec 15 1990

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erbB-1 Genes
Epidermal Growth Factor Receptor
Heterografts
Glioma
Cell Line
Genes
Cultured Cells
Serial Passage
Biopsy
Pancreatic Ribonuclease
Radioligand Assay
Messenger RNA
Gene Dosage
Gene Rearrangement
Gene Amplification
Glioblastoma
Immunoprecipitation
Nude Mice
Proteins
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bigner, S. H., Humphrey, P. A., Wong, A. J., Vogelstein, B., Mark, J., Friedman, H. S., & Vogelstein, B. (1990). Characterization of the epidermal growth factor receptor in human glioma cell lines and xenografts. Cancer Research, 50(24), 8017-8022.

Characterization of the epidermal growth factor receptor in human glioma cell lines and xenografts. / Bigner, Sandra H.; Humphrey, Peter A.; Wong, Albert J.; Vogelstein, Bert; Mark, Joachim; Friedman, Henry S.; Vogelstein, Bert.

In: Cancer Research, Vol. 50, No. 24, 15.12.1990, p. 8017-8022.

Research output: Contribution to journalArticle

Bigner, SH, Humphrey, PA, Wong, AJ, Vogelstein, B, Mark, J, Friedman, HS & Vogelstein, B 1990, 'Characterization of the epidermal growth factor receptor in human glioma cell lines and xenografts', Cancer Research, vol. 50, no. 24, pp. 8017-8022.
Bigner SH, Humphrey PA, Wong AJ, Vogelstein B, Mark J, Friedman HS et al. Characterization of the epidermal growth factor receptor in human glioma cell lines and xenografts. Cancer Research. 1990 Dec 15;50(24):8017-8022.
Bigner, Sandra H. ; Humphrey, Peter A. ; Wong, Albert J. ; Vogelstein, Bert ; Mark, Joachim ; Friedman, Henry S. ; Vogelstein, Bert. / Characterization of the epidermal growth factor receptor in human glioma cell lines and xenografts. In: Cancer Research. 1990 ; Vol. 50, No. 24. pp. 8017-8022.
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