Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin

Abstract

Epidermal growth factor (EGF), through interaction with specific cell surface receptors, generates a pleiotropic response that, by a poorly defined mechanism, can induce proliferation of target cells. Subversion of the EGF mitogenic signal through expression of a truncated receptor may be involved in transformation by the avian erythroblastosis virus (AEV) oncogene v-erb-B, suggesting that similar EGF receptor defects may be found in human neoplasias. Overexpression of EGF receptors has been reported on the epidermoid carcinoma cell line A431, in various primary brain tumours and in squamous carcinomas. In A431 cells the receptor gene is amplified. Here we show that 4 of 10 primary brain tumours of glial origin which express levels of EGF receptors that are higher than normal also have amplified EGF receptor genes. Amplified receptor genes were not detected in the other brain tumours examined. Further analysis of EGF receptor defects may show that such altered expression and amplification is a particular feature of certain human tumours.

Notch1 signaling promotes survival of glioblastoma cells via EGFR-mediated induction of anti-apoptotic Mcl-1

“…28 Further, activation of the Figure S6D). Furthermore, the siRNA-mediated downregulation of EGFR resulted in significantly reduced colony formation in a clonogenicity assay (Supplementary Figure S7) suggesting that Notch1-mediated EGFR regulation contributes to the Notch1-dependent modulation of proliferation.…”

Relationship of p215BRCA1 to tyrosine kinase signaling pathways and the cell cycle in normal and transformed cells

“…Results were also separately con®rmed using scanning densitometry. In U87MG cells, the EGFr is overexpressed and appears to mediate the transformed phenotype (Libermann et al, 1985;Nishikawa et al, 1994). In U87/T691 cells, the T691stop mutant proteins heterodimerize with the EGF receptor, suppressing transformation characteristics of these tumor cells (O'Rourke et al, 1997).…”

Analysis of epidermal growth factor receptor and activated epidermal growth factor receptor expression in pituitary adenomas and carcinomas

“…Exceptions to this observation include gliomas and squamous cell carcinomas, which show amplification of EGFR. 8 While in some studies EGFR expression has been correlated with markers of clinical aggression, 9-11 a recent meta-analysis indicated that EGFR expression was rarely related to clinical outcome. 12 Yet another study suggested that phosphorylation of EGFR, but not its overexpression, might be associated with a poor prognosis.…”