Autocrine and paracrine factors, including glutamate and epidermal growth factor (EGF), are potent inducers of brain tumor cell invasion, a pathological hallmark of malignant gliomas.
PKM2-regulated MLC2 phosphorylation, which is greatly enhanced by EGF stimulation or EGFRvIII, K-Ras G12V and B-Raf V600E mutant expression, plays a pivotal role in cytokinesis, cell proliferation and brain tumour development.
Here, we show the first example of this alternate mechanism in brain tumors by showing that EGF receptor (EGFR)-mutant glioblastomas (GBMs) evade EGFR TKIs by transcriptionally de-repressing platelet-derived growth factor receptor β (PDGFRβ).
The purpose of this study was to investigate the association between the single-nucleotide polymorphism of EGF+61G/A and extraaxial brain tumors in a population of the southeast of Brazil.
One prominent molecular abnormality discovered in these astrocytic brain tumors is alteration of epidermal growth factor (EGF) receptor (EGFR) through gene amplification and/or mutation resulting in excessive signaling from this receptor.
The authors have previously shown that DAB(389)EGF is selectively toxic to EGFR-overexpressing cells, including human brain tumour and lung carcinoma cell lines.
Peptide radiopharmaceuticals such as radiolabeled EGF could be used to image early brain tumors, should these radiopharmaceuticals be made transportable through the BBB.
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.