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Radiation-induced Notch signaling in breast cancer stem cells

Radiation-induced Notch signaling in breast cancer stem cells

International Journal of Radiation Oncology, Biology, Physics 87(3): 609-618

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. 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. 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. 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.

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Accession: 055345022

Download citation: RISBibTeXText

PMID: 23992604

DOI: 10.1016/j.ijrobp.2013.06.2064

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