Abstract 3367: Breast cancer stem cell-like cells are sensitive to ionizing radiation: Role of ATM

Abstract

Abstract The aim of this study was to determine the radiosensitivity of cancer stem (tumor-initiating) cells (CSC), which are known to be responsible for tumorogenicity and metastasis. We used breast cancer stem cell (CSC)-like MDA-MB231 and MDA-MB453 cell lines which were established by Dr. Edward V. Prochownik (Sajithlal et al., Stem Cells, 28:1008, 2010). Interestingly, these cells can proliferate without differentiation and have characteristics of tumor-initiating cells. CSC-like cells and their alternate subset non-CSC cells were exposed to α-rays (1.25-8.75Gy) and survival curves were determined by colony formation. A final slope, D0, of the survival curve for each cell line was determined to measure radiosensitivity. D0 of CSC-like MDA-MB453 cells and that of non-CSC MDA-MB453 cells were 1.16 Gy and 1.55 Gy, respectively. Similar results were observed in MDA-MB231 cells. We further examined whether CSC-like cells are relatively radiosensitive owing to different intrinsic factors including cell cycle distribution, free-radical scavengers and DNA repair. We observed that, unlike non-CSC cells, CSC-like cells have little/no sublethal damage repair and a low intracellular level of ATM. These results suggest that low DNA repair capability is responsible for the high radiosensitivity of these CSC-like cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3367. doi:1538-7445.AM2012-3367