PMID- 15450724
OWN - NLM
STAT- MEDLINE
DCOM- 20050225
LR  - 20181130
IS  - 0167-8140 (Print)
IS  - 0167-8140 (Linking)
VI  - 72
IP  - 3
DP  - 2004 Sep
TI  - Radiation-induced activation of a common variant of EGFR confers enhanced 
      radioresistance.
PG  - 267-73
AB  - BACKGROUND AND PURPOSE: The type-III EGFR variant (EGFRvIII) is known to promote 
      enhanced tumorigenicity. We have previously defined the importance of EGFRvIII in 
      cellular radiation responses using Chinese hamster ovary cells (CHO). In the 
      current study, we have extended our investigations of EGFRvIII to human tumor 
      cells in vitro and in vivo and further verified the important role of EGFRvIII in 
      modulating radiosensitivity. MATERIAL AND METHODS: The cell lines MDA-MB-231, 
      U-87 MG, A-431 and U-373 MG were used. Adenoviral (Ad) vectors were produced to 
      overexpress EGFRvIII in vitro or in xenograft tumors in vivo. The EGFR, EGFRvIII 
      expression and tyrosine phosphorylation (Tyr-P) levels were quantified by Western 
      blotting. The relative radiosensitivities were assessed in vitro by standard 
      colony formation and in vivo by tumor growth delay assays. RESULTS: The presence 
      of EGFRvIII was verified in all xenograft tumors tested with no detectable 
      expression in the corresponding cells under in vitro culture conditions. 
      MDA-MB-231 xenograft tumors demonstrated EGFRvIII expression levels, which were 
      1.9-fold higher relative to EGFRwt compared to a 14.5-fold higher Tyr-P. Ionizing 
      radiation of these tumors at 4 Gy induced an average 3.2-fold increase in 
      EGFRvIII Tyr-P. EGFRvIII expression in U-373 MG cells significantly enhanced 
      survival after 4Gy, which was completely abolished by dominant-negative 
      EGFR-CD533. Finally, the ability of EGFRvIII to accelerate tumor growth during 
      irradiation was confirmed in vivo. CONCLUSION: EGFRvIII is frequently expressed 
      in a variety of different tumor types and can confer significant radioresistance, 
      thus further providing evidence for EGFRvIII as an additional important target in 
      our approaches to radiosensitize malignant solid tumors.
FAU - Lammering, Guido
AU  - Lammering G
AD  - Department of Radiation Oncology, Medical College of Virginia, Virginia 
      Commonwealth University, Richmond, VA, USA.
FAU - Valerie, Kristoffer
AU  - Valerie K
FAU - Lin, Peck-Sun
AU  - Lin PS
FAU - Hewit, Theodore H
AU  - Hewit TH
FAU - Schmidt-Ullrich, Rupert K
AU  - Schmidt-Ullrich RK
LA  - eng
GR  - P01CA72955/CA/NCI NIH HHS/United States
GR  - R01CA65896/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Ireland
TA  - Radiother Oncol
JT  - Radiotherapy and oncology : journal of the European Society for Therapeutic 
      Radiology and Oncology
JID - 8407192
RN  - 0 (epidermal growth factor receptor VIII)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Animals
MH  - ErbB Receptors/analysis/metabolism/*physiology
MH  - Humans
MH  - Mice
MH  - Neoplasm Transplantation
MH  - Phosphorylation
MH  - Radiation Tolerance/*drug effects
MH  - Transplantation, Heterologous
MH  - Tumor Cells, Cultured
MH  - Tyrosine/metabolism
EDAT- 2004/09/29 05:00
MHDA- 2005/02/26 09:00
CRDT- 2004/09/29 05:00
PHST- 2004/05/28 00:00 [received]
PHST- 2004/06/26 00:00 [revised]
PHST- 2004/06/28 00:00 [accepted]
PHST- 2004/09/29 05:00 [pubmed]
PHST- 2005/02/26 09:00 [medline]
PHST- 2004/09/29 05:00 [entrez]
AID - S0167-8140(04)00297-X [pii]
AID - 10.1016/j.radonc.2004.07.004 [doi]
PST - ppublish
SO  - Radiother Oncol. 2004 Sep;72(3):267-73. doi: 10.1016/j.radonc.2004.07.004.