Department of Radiation Oncology, University of Colorado School of Medicine, Aurorao, CO 80010, USA.
Int J Hyperthermia. 2011;27(5):427-34. doi: 10.3109/02656736.2011.566593.
To examine the molecular mechanism of cellular EGFR activation during hyperthermia treatment.
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.
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.
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.
研究热疗过程中细胞表皮生长因子受体（EGFR）激活的分子机制。
采用最近开发的基于双荧光素酶的 EGFR 报告系统来量化肿瘤细胞中的 EGR 活性，该系统允许我们以非侵入性的方式在体外和体内监测 EGFR 的激活。
我们发现，热疗处理 MDA-MB231 乳腺癌细胞可导致组织培养和异种移植瘤中 EGFR 活性的强烈诱导。此外，我们发现这种诱导是由热休克蛋白 Hsp90 介导的。特异性 Hsp90 抑制剂格尔德霉素的给药以及针对 HSP90 的 RNAi 有效地抑制了 EGFR 的激活，表明 Hsp90 在热诱导的 EGFR 激活中起关键作用。此外，用格尔德霉素处理的细胞对热疗敏感，这表明在热疗方案中添加 Hsp90 抑制剂可能对癌症治疗有有益的效果。
我们的生物发光成像报告系统为研究体外和体内热疗诱导的 EGFR 激活提供了有力的工具。Hsp90 被发现是介导肿瘤细胞中热诱导的 EGFR 激活的关键因素。
