title: Epidermal growth factor receptor pathway gene expressions and biological response of glioblastoma multiforme cell lines to erlotinib.
abstract: BACKGROUND
  Erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, exerts highly variable antiproliferative effects on human glioblastoma multiforme (GBM) cells in vitro and in vivo. As these effects are independent of EGFR baseline expression levels, more complex genetic signatures may form the molecular basis of the erlotinib-sensitive and erlotinib-resistant GBM phenotypes. The aim of the current study was to determine which genes within the EGFR signaling pathway are candidates for mediating the cellular response of human GBM towards erlotinib.
  
  
  METHODS
  Complementary (c)RNAs from cell lines selected to represent the sensitive, intermediately responsive and resistant phenotypes, respectively, were hybridized to CodeLink Human Whole Genome Bioarrays.
  
  
  RESULTS
  Expression analysis of the prospectively selected 244 genes whose products constitute the EGFR signaling pathway identified five genes the expression of which significantly correlated with phenotype. Functional annotation analysis revealed one (STATI) and two (FKBP14, RAC1) genes conclusively associated with sensitivity and resistance to erlotinib, respectively. Moreover, two additional genes (PTGER4, MYC) were unexpectedly found to be associated with sensitivity. The gene expressions were confirmed by quantitative polymerase chain reaction.
  
  
  CONCLUSIONS
  Five genes within the EGFR signaling pathway may modulate GBM response to erlotinib, which further emphasizes the importance of this pathway for the biology of GBM.
authors.affiliation: Department of Neurosurgery, Ruprecht Karls University, Im Neuenheimer Feld 400, D-69120 Heidelberg, Germany. marc.halatsch@med.uni-heidelberg.de
authors.forename: Marce E
authors.initials: ME
authors.lastname: Halatsch
authors.forename: Sarah
authors.initials: S
authors.lastname: Löw
authors.forename: Thomas
authors.initials: T
authors.lastname: Hielscher
authors.forename: Ursula
authors.initials: U
authors.lastname: Schmidt
authors.forename: Andreas
authors.initials: A
authors.lastname: Unterberg
authors.forename: Vassilios I
authors.initials: VI
authors.lastname: Vougioukas
mesh_terms: D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000069347:Erlotinib Hydrochloride; D015870:Gene Expression; D018773:Genes, erbB-1; D016259:Genes, myc; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D018078:Receptors, Prostaglandin E / Q000096:biosynthesis / Q000235:genetics; D058309:Receptors, Prostaglandin E, EP4 Subtype; D050794:STAT1 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D022021:Tacrolimus Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D020830:rac1 GTP-Binding Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: C545650:PTGER4 protein, human; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C107953:RAC1 protein, human; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D020830:rac1 GTP-Binding Protein; D022021:Tacrolimus Binding Proteins