Uniform MDM2 overexpression in a panel of glioblastoma multiforme cell lines with divergent EGFR and p53 expression status.
BACKGROUND
Overexpression and deletion mutation of the epidermal growth factor receptor (EGFR) gene, as well as murine double minute 2 (MDM2) overexpression have been linked to the absence of p53 gene mutations in human glioblastoma multiforme (GBM).


METHODS
EGFR and MDM2 messenger (m)RNA expression profiles and p53 status were examined by reverse transcription-polymerase chain rection (RT-PCR) and gene sequencing, respectively, in a set of human wild-type (wt) p53 GBM cell lines (U-87MG, U-87MG.wtEGFR and U-87MG.deltaEGFR) that exclusively differ in EGFR expression (endogenous wt EGFR expression, exogenous wt EGFR overexpression and exogenous 801-bp deletion-mutant [delta] EGFR overexpression, respectively), as well as in two human mutant p53 GBM cell lines that differ approximately two-fold in endogenous wt EGFR mRNA expression.


RESULTS
Regardless of the underlying heterogeneity in EGFR mRNA expression and p53 status, MDM2 was similarly overexpressed among the cell lines.


CONCLUSIONS
These data suggest that in human GBM (i) overexpression of wt or deltaEGFR and of MDM2 may constitute independent genetic events, (ii) overexpression of wt EGFR and mutation of p53 in GBM, although considered mutually exclusive in vivo, are not reciprocally prohibitive per se, and (iii) p53 mutations do not necessarily preclude MDM2 overexpression. In addition, this set of human GBM cell lines may constitute a suitable model for evaluating MDM2-targeted therapies in the context of various accompanying genetic alterations.
Halatsch
Marc E
ME
Department of Neurosurgery, Ruprecht Karls University, Im Neuenheimer Feld 400, D-69120 Heidelberg, Germany. marc.halatsch@med.uni-heidelberg.de
Schmidt
Ursula
U
Unterberg
Andreas
A
Vougioukas
Vassilios I
VI
D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D016158:Genes, p53; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D066246:ErbB Receptors