Irradiated human breast cancer cells treated with steroid hormones are enriched with cancer stem cells

Exposure to ionizing radiation is known to result in an increased risk of breast cancer. There is strong evidence that steroid hormones influence radiosensitivity and breast cancer risk. Tumors may be initiated by a small subpopulation of cancer stem cells. In order to assess whether the modulation of radiation-induced breast cancer risk by steroid hormones might involve cancer stem cells, we measured by flow cytometry the proportion of cancer stem-like cells (CSCs) in irradiated T47D and MCF7 breast cancer cell lines after progesterone and estrogen treatment. We isolated a subpopulation of CSCs with high aldehyde dehydrogenase (ALDH) activity and increased ability to form tumorspheres in suspension cultures. Progesterone treatment inhibited radiation-induced cell death in both cell lines, while estrogen treatment counteracted radiation-induced cell death only in T47D cells. Exposure to ionizing radiation and estrogen treatment of non-irradiated T47D cells resulted in increased percentages of CSCs with higher tumorigenic properties. Progesterone treatment of both irradiated and non-irradiated T47D cells increased the proportion of CSCs, suggesting that progesterone might influence radiosensitivity in the breast partly by triggering the expansion of the cancer stem cell compartment.ISSCR 10th Annual Meetin