Progesterone generates breast cancer stem cells through PR-independent mechanisms in irradiated human mammary cell lines

Chest radiation exposure was shown to increase breast cancer risk. Steroid hormones are known to influence radiosensitivity and breast cancer risk. Tumors may be initiated by a small subpopulation of cancer stem cells (CSCs). In order to evaluate whether the modulation of radiation-induced breast cancer risk by steroid hormones could involve CSCs, we measured the proportion of ALDH+ and CD44+/CD24- CSCs in irradiated breast cancer cell lines after steroid hormone treatment. Progesterone stimulated the expansion of the CSC compartment both in PR+ breast cancer cells and in PR- normal cells. In MCF10A normal epithelial PR- cells, progesterone treatment and irradiation triggered cancer and stemness-associated microRNA regulations (such as the down-regulation of miR-22 and miR-29c expression), which resulted in increased proportions of radiation-resistant CSCs. Thus progesterone might influence radiation-induced breast cancer risk by generating tumor-initiating breast CSCs through nuclear PR-independent mechanisms, such as membrane progesterone receptors.第73回日本癌学会学術総会に参加し、発表する