Generation of breast cancer stem cells by steroid hormones in irradiated human mammary cell lines

Guillaume Vares; Xing Cui; Bing Wang; Tetsuo Nakajima; Mitsuru Nenoi

doi:10.1371/journal.pone.0077124

Generation of breast cancer stem cells by steroid hormones in irradiated human mammary cell lines

PLoS One. 2013 Oct 16;8(10):e77124. doi: 10.1371/journal.pone.0077124. eCollection 2013.

Authors

Guillaume Vares¹, Xing Cui, Bing Wang, Tetsuo Nakajima, Mitsuru Nenoi

Affiliation

¹ Research Center for Radiation Protection, National Institute of Radiological Sciences, Chiba, Japan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aldehyde Dehydrogenase / metabolism
Breast Neoplasms / genetics
Breast Neoplasms / metabolism*
Cell Death / drug effects
Cell Death / radiation effects
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Proliferation / radiation effects
Cell Survival / drug effects
Cell Survival / radiation effects
Cluster Analysis
Dose-Response Relationship, Radiation
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic / drug effects
Gene Expression Regulation, Neoplastic / radiation effects
Gonadal Steroid Hormones / pharmacology*
Humans
MicroRNAs / genetics
Neoplastic Stem Cells / drug effects*
Neoplastic Stem Cells / metabolism*
Neoplastic Stem Cells / radiation effects
Radiation Tolerance
Reactive Oxygen Species / metabolism
X-Rays

Substances

Gonadal Steroid Hormones
MicroRNAs
Reactive Oxygen Species
Aldehyde Dehydrogenase

Grants and funding

This study was funded by JSPS KAKENHI Grant Number 24710066. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.