Overexpression of deletion-mutant epidermal growth factor receptor is associated with altered genotoxic stress-provoked p53 mRNA induction in a humanglioblastoma cell line

A distinct 801-bp deletion mutation of the epidermal growth factor receptor (EGFR) gene is frequently present in primary glioblastoma multiforme (GBM) , confers enhanced tumorigenicity in vivo and is prognostic of a shorter in terval to clinical relapse. This study sought to investigate whether overex pression of deletion-mutant (Delta) EGFR affects genotoxic stress-provoked mRNA inductions of p53 and murine double minute 2 (MDM2), two other genes s trongly involved in the pathogenesis of GBM. In a set of human wild-type (w t) p53 CBM cell lines (U-87MG and U-87MC.Delta EGFR) that exclusively diffe r in EGFR expression (endogenous wt EGFR expression and exogenous Delta EGF R overexpression, respectively), ultraviolet (UV) light irradiation-mediate d EGFR, p53 and MDM2 genotoxic stress-provoken mRNA inductions were assesse d by semiquantitative reverse transcription-polymerase chain reaction (RT-P CR) and densitometry of electrophoretically separated and stained RT-PCR pr oducts. Although baseline (at 0 J/m(2)) p53 mRNA expression in U-87MG.Delta EGFR was 42-fold reduced, maximum p53 induction (at 8 J/m(2)) amounted to 130% compared to U-87MG. Thus, ultimate UV light-mediated p53 mRNA inductio n was 131.5-fold in U-87MG.Delta EGFR and 2.8-fold in U-87MG. In contrast, neither wt/Delta EGFR not MDM2 mRNA expressions were significantly inducibl e, and MDM2 mRNA profiles were essentially the same among U-87MG and U-87MG .Delta EGFR. These data suggest that in human GBM overexpression of Delta E GFX is associated with differential genotoxic stress-provoked p53 mRNA indu ction whereas MDM2 mRNA expression is apparantly not directly affected by E GFR status.