title: Generation of breast cancer stem cells by steroid hormones in irradiated human mammary cell lines.
abstract: Exposure to ionizing radiation was shown 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 (CSCs). In order to assess whether the modulation of radiation-induced breast cancer risk by steroid hormones could involve CSCs, we measured by flow cytometry the proportion of CSCs in irradiated breast cancer cell lines after progesterone and estrogen treatment. Progesterone stimulated the expansion of the CSC compartment both in progesterone receptor (PR)-positive breast cancer cells and in PR-negative normal cells. In MCF10A normal epithelial PR-negative cells, progesterone-treatment and irradiation triggered cancer and stemness-associated microRNA regulations (such as the downregulation of miR-22 and miR-29c expression), which resulted in increased proportions of radiation-resistant tumor-initiating CSCs.
authors.affiliation: Research Center for Radiation Protection, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Vares
authors.forename: Xing
authors.initials: X
authors.lastname: Cui
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nakajima
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Nenoi
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D016000:Cluster Analysis; D004307:Dose-Response Relationship, Radiation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism* / Q000528:radiation effects; D011836:Radiation Tolerance; D017382:Reactive Oxygen Species / Q000378:metabolism; D014965:X-Rays
chemical_list: D012739:Gonadal Steroid Hormones; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D000444:Aldehyde Dehydrogenase