Function of aberrant EGFR in malignant gliomas.
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.
Sugawa
N
N
Department of Neurosurgery, Kyoto Prefectural Yosanoumi Hospital, Japan.
Yamamoto
K
K
Ueda
S
S
Morita
N
N
Kita
M
M
Nishino
H
H
Fushiki
S
S
Okabe
T
T
D000818:Animals; D034961:Antigens, Nuclear; D017209:Apoptosis; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D019394:Ki-67 Antigen; D051379:Mice; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D034961:Antigens, Nuclear; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D066246:ErbB Receptors