title: Cellular and tumor radiosensitivity is correlated to epidermal growth factor receptor protein expression level in tumors without EGFR amplification.
abstract: OBJECTIVE
  There is conflicting evidence for whether the expression of epidermal growth factor receptor in human tumors can be used as a marker of radioresponse. Therefore, this association was studied in a systematic manner using squamous cell carcinoma (SCC) cell lines grown as cell cultures and xenografts.
  
  
  METHODS
  The study was performed with 24 tumor cell lines of different tumor types, including 10 SCC lines, which were also investigated as xenografts on nude mice. Egfr gene dose and the length of CA-repeats in intron 1 were determined by polymerase chain reaction, protein expression in vitro by Western blot and in vivo by enzyme-linked immunosorbent assay, and radiosensitivity in vitro by colony formation. Data were correlated with previously published tumor control dose 50% data after fractionated irradiation of xenografts of the 10 SCC.
  
  
  RESULTS
  EGFR protein expression varies considerably, with most tumor cell lines showing moderate and only few showing pronounced upregulation. EGFR upregulation could only be attributed to massive gene amplification in the latter. In the case of little or no amplification, in vitro EGFR expression correlated with both cellular and tumor radioresponse. In vivo EGFR expression did not show this correlation.
  
  
  CONCLUSIONS
  Local tumor control after the fractionated irradiation of tumors with little or no gene amplification seems to be dependent on in vitro EGFR via its effect on cellular radiosensitivity.
authors.affiliation: Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Hubertus Wald Tumor Center, Hamburg, Germany.
authors.forename: Ulla
authors.initials: U
authors.lastname: Kasten-Pisula
authors.forename: Jarob
authors.initials: J
authors.lastname: Saker
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eicheler
authors.forename: Mechthild
authors.initials: M
authors.lastname: Krause
authors.forename: Ala
authors.initials: A
authors.lastname: Yaromina
authors.forename: Sönke
authors.initials: S
authors.lastname: Meyer-Staeckling
authors.forename: Benjamin
authors.initials: B
authors.lastname: Scherkl
authors.forename: Malte
authors.initials: M
authors.lastname: Kriegs
authors.forename: Burkhard
authors.initials: B
authors.lastname: Brandt
authors.forename: Reidar
authors.initials: R
authors.lastname: Grénman
authors.forename: Cordula
authors.initials: C
authors.lastname: Petersen
authors.forename: Michael
authors.initials: M
authors.lastname: Baumann
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Dikomey
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D005784:Gene Amplification; D018773:Genes, erbB-1 / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D011836:Radiation Tolerance / Q000235:genetics; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors