Radiation-induced Notch signaling in breast cancer stem cells.

ABSTRACT

PURPOSE: To explore patterns of Notch receptor and ligand expression in response to radiation that could be crucial in defining optimal dosing schemes for γ-secretase inhibitors if combined with radiation. METHODS AND MATERIALS Using MCF-7 and T47D breast cancer cell lines, we used real-time reverse transcription-polymerase chain reaction to study the Notch pathway in response to radiation. RESULTS: We show that Notch receptor and ligand expression during the first 48 hours after irradiation followed a complex radiation dose-dependent pattern and was most pronounced in mammospheres, enriched for breast cancer stem cells. Additionally, radiation activated the Notch pathway. Treatment with a γ-secretase inhibitor prevented radiation-induced Notch family gene expression and led to a significant reduction in the size of the breast cancer stem cell pool. CONCLUSIONS: Our results indicate that, if combined with radiation, γ-secretase inhibitors may prevent up-regulation of Notch receptor and ligand family members and thus reduce the number of surviving breast cancer stem cells.