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Function of aberrant EGFR in malignant gliomas
1Department of Neurosurgery, Kyoto Prefectural Yosanoumi Hospital, Japan.
Abstract:
The most common alteration of the epidermal growth factor receptor (EGFR) gene in human malignant gliomas is an in-frame deletion of exon 2-7 from the extra-cellular domain. To study the relationship between the expression of this aberrant EGFR and cell proliferation, as well as apoptosis in malignant gliomas, we have developed U-87MG cell transfectants that express the aberrant (mutant-type) or normal (wild-type) EGFR. We analyzed cell number, tumor volume, and MIB-1 positive rate as proliferation markers, and found that in tissue culture, tumors derived from U-87 MG cells (mutant-type) have the same proliferative activity as those derived from U-87 MG cells (wild-type). However, when cells expressing mutant EGFR were implanted into nude mice subcutaneously, the tumorigenic capacity was much enhanced. We also found that the apototic index of tumors derived from U-87 MG cells (mutant-type) was less than 0.1%, whereas that of wild-type tumor was 1%. These results suggest that aberrant EGFR affects the malignancy of glioma by stimulating proliferation and inhibiting apoptosis.
Insights
Aberrant epidermal growth factor receptor (EGFR) enhances malignant glioma growth by increasing proliferation and reducing apoptosis. This study utilized U-87MG cell transfectants to investigate mutant-type EGFR's impact on glioma malignancy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Malignant gliomas frequently exhibit epidermal growth factor receptor (EGFR) gene alterations.
- An in-frame deletion of exon 2-7 in the EGFR extracellular domain is a common mutation.
Purpose of the Study:
- To investigate the role of aberrant EGFR expression in malignant glioma cell proliferation and apoptosis.
- To compare the effects of mutant-type EGFR versus wild-type EGFR on glioma development.
Main Methods:
- Developed U-87MG cell transfectants expressing either mutant-type or wild-type EGFR.
- Assessed proliferation using cell number, tumor volume, and MIB-1 positive rates.
- Evaluated apoptosis via apoptotic index measurements.
Main Results:
- In vitro, both mutant-type and wild-type EGFR-expressing U-87MG cells showed similar proliferation rates.
- Subcutaneous implantation in nude mice revealed significantly enhanced tumorigenic capacity in cells expressing mutant EGFR.
- Tumors with mutant EGFR had a markedly lower apoptotic index (<0.1%) compared to wild-type tumors (1%).
Conclusions:
- Aberrant EGFR expression significantly promotes malignant glioma progression.
- Mutant-type EGFR stimulates proliferation and inhibits apoptosis, contributing to increased glioma malignancy.