In view of the similarity to the activated viral and cellular erbB genes in the avian system, these mutated and overexpressed EGF receptors might play a role in the onset or development of human glioblastoma cells.
These data indicate that overexpression of the EGF receptor and mutations of the p53 tumor suppressor gene are mutually exclusive events defining two different genetic pathways in the evolution of glioblastoma as the common phenotypic endpoint.
Here we report the development and selection for a rearranged amplified EGF receptor, which lacks cytoplasmic amino acid sequences in a human glioblastoma xenograft.
Kinase-deficient erbB proteins reduced epidermal growth factor (EGF)-induced tyrosine phosphorylation of endogenous Shc proteins and also reduced immediate and sustained EGF-induced ERK MAPK activities in human glioblastoma cells, although basal ERK MAPK activities were unaffected.
The atypical protein kinase C inhibitor induced rapid apoptosis in glioblastoma cells expressing EGFRvIII and killed these cells with an IC50 of 16 microM.
A glioblastoma stem cell (GSC) line, GSC11, grows as neurospheres in serum-free media supplemented with EGF (epidermal growth factor) and bFGF (basic fibroblast growth factor), and, if implanted in nude mice brains, will recapitulate high-grade glial tumors.
SNAI2 mRNA expression correlated with histologic grade and invasive phenotype in primary human glioma specimens, and was induced by EGF receptor activation in human glioblastoma cells.
A bispecific ligand-directed toxin (BLT), called EGFATFKDEL, consisting of human epidermal growth factor, a fragment of urokinase, and truncated pseudomonas exotoxin (PE38) was assembled in order to target human glioblastoma.
In addition, ectopic expression of α-catenin or depletion of β-catenin suppresses EGF-promoted glioblastoma cell migration, invasion, and proliferation.
Epidermal growth factor module-containing mucin-like receptor 2 is a newly identified adhesion G protein-coupled receptor associated with poor overall survival and an invasive phenotype in glioblastoma.