Contrasting in vivo and in vitro fates of glioblastoma cell subpopulations with amplified EGFR
- 17 October 2003
- journal article
- research article
- Published by Wiley in Genes, Chromosomes and Cancer
- Vol. 39 (1), 29-36
- https://doi.org/10.1002/gcc.10300
Abstract
Despite the high incidence of EGFR amplification in patient glioblastoma multiforme (GBM) tissues, only a single GBM cell line, of the many described in the literature, is known to contain and maintain amplified EGFR. Because EGFR mutations in GBM manifest primarily, if not exclusively, in amplified form, it follows that the availability of cell lines with mutation of endogenous EGFR would also be in short supply. In fact, there are no GBM cell lines harboring the common EGFR mutants described in patient GBMs. These observations suggest that in vivo environments select for EGFR amplification, whereas in vitro environments, specifically cell cultures, select against this gene alteration. To contrast directly the fates of EGFR amplification in vivo and in vitro, as well as to examine potential relationships between EGFR amplification and mutation, we have established and maintained GBM explants as xenografts by serial passaging in nude mice. Analysis of EGFR copy number and EGFR mutation status in 11 patient tumors and their corresponding xenografts, as well as the monitoring of EGFR copy number during the establishment of a GBM cell line from a xenograft with amplified EGFR, indicated that selection for EGFR amplification is an in vivo phenomenon. Furthermore, our data indicated that EGFR mutation occurs only in tumors with EGFR amplification and showed that the selection of amplified mutant EGFR over amplified wild‐type EGFR as a xenograft occurred rapidly and completely during tumor propagation.Keywords
This publication has 18 references indexed in Scilit:
- TGF-α-Driven Tumor Growth Is Inhibited by an EGF Receptor Tyrosine Kinase InhibitorBiochemical and Biophysical Research Communications, 2002
- The Protein Tyrosine Phosphatase TCPTP Suppresses the Tumorigenicity of Glioblastoma Cells Expressing a Mutant Epidermal Growth Factor ReceptorOnline Journal of Public Health Informatics, 2001
- Linking molecular therapeutics to molecular diagnostics: Inhibition of the FRAP/RAFT/TOR component of the PI3K pathway preferentially blocks PTEN mutant cells in vitro and in vivoProceedings of the National Academy of Sciences of the United States of America, 2001
- Treatment of the T98G Glioblastoma Cell Line with Antisense Oligonucleotides Directed Toward mRNA Encoding Transforming Growth Factor-α and the Epidermal Growth Factor ReceptorMedical Oncology, 2001
- Acquired Rearrangement of an Amplified Epidermal Growth Factor Receptor (EGFR) Gene in a Human Glioblastoma XenograftJournal of Neuropathology and Experimental Neurology, 1999
- Analysis of glioma cell lines for amplification and overexpression of MDM2Genes, Chromosomes and Cancer, 1994
- Anti-synthetic peptide antibody reacting at the fusion junction of deletion-mutant epidermal growth factor receptors in human glioblastoma.Proceedings of the National Academy of Sciences of the United States of America, 1990
- Amplification of the structurally and functionally altered epidermal growth factor receptor gene (c-erbB) in human brain tumors.Molecular and Cellular Biology, 1988
- Amplified, overexpressed and rearranged epidermal growth factor receptor gene in a human astrocytoma cell lineBiochemical and Biophysical Research Communications, 1985
- Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial originNature, 1985