Non-invasive, quantitative monitoring of hyperthermia-induced EGFR activation in xenograft tumours.

Published

Journal Article

PURPOSE: To examine the molecular mechanism of cellular EGFR activation during hyperthermia treatment. MATERIALS AND 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.

Full Text

Duke Authors

Cited Authors

  • Wolf, F; Li, W; Li, F; Li, C-Y

Published Date

  • 2011

Published In

Volume / Issue

  • 27 / 5

Start / End Page

  • 427 - 434

PubMed ID

  • 21756040

Pubmed Central ID

  • 21756040

Electronic International Standard Serial Number (EISSN)

  • 1464-5157

Digital Object Identifier (DOI)

  • 10.3109/02656736.2011.566593

Language

  • eng

Conference Location

  • England