title: Non-invasive, quantitative monitoring of hyperthermia-induced EGFR activation in xenograft tumours.
abstract: OBJECTIVE
  To examine the molecular mechanism of cellular EGFR activation during hyperthermia treatment.
  
  
  METHODS
  EGR activities in tumour cells were quantified through the use of a recently developed split-luciferase-based EGFR reporter system which allowed us to monitor EGFR activation in vitro as well as in vivo in a non-invasive manner.
  
  
  RESULTS
  We found that hyperthermia treatment of MDA-MB231 breast cancer cells resulted in a strong induction of EGFR activity in tissue culture as well as in xenograft tumours. Furthermore, we found that this induction is mediated by the heat shock protein Hsp90. Administration of the specific Hsp90 inhibitor geldanamycin as well as RNAi directed against HSP90 effectively inhibited EGFR activation, suggesting an essential role for Hsp90 in hyperthermia-induced EGFR activation. In addition, cells treated with geldanamycin were sensitised to heat treatment, suggesting that adding Hsp90 inhibitors to hyperthermia regimens might have a beneficial effect for cancer treatment.
  
  
  CONCLUSIONS
  Our bioluminescent imaging reporter provided a powerful tool to examine hyperthermia-induced EGFR activation in vitro as well as in vivo. Hsp90 was found to be a key factor mediating heat-induced EGFR activation in tumour cells.
authors.affiliation: Department of Radiation Oncology, University of Colorado School of Medicine, Aurorao, CO 80010, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Wolf
authors.forename: Wenrong
authors.initials: W
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Chuan-Yuan
authors.initials: CY
authors.lastname: Li
mesh_terms: D000818:Animals; D016227:Benzoquinones; D001943:Breast Neoplasms / Q000628:therapy; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006979:Hyperthermia, Induced; D047029:Lactams, Macrocyclic; D051379:Mice; D014183:Transplantation, Heterologous
chemical_list: D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D066246:ErbB Receptors; C001277:geldanamycin