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Steroid Hormones, Steroid Receptors, and Breast Cancer Stem Cells

  • Jessica Finlay-Schultz
  • Carol A. Sartorius
Article

Abstract

The ovarian hormones progesterone and estrogen play important roles in breast cancer etiology, proliferation, and treatment. Androgens may also contribute to breast cancer risk and progression. In recent years, significant advances have been made in defining the roles of these steroid hormones in stem cell homeostasis in the breast. Stem cells are potential origins of breast cancer and may dictate tumor phenotype. At least a portion of breast cancers are proposed to be driven by cancer stem cells (CSCs), cells that mimic the self-renewing and repopulating properties of normal stem cells, and can confer drug resistance. Progesterone has been identified as the critical hormone regulating normal murine mammary stem cell (MaSC) populations and normal human breast stem cells. Synthetic progestins increase human breast cancer risk; one theory speculates that this occurs through increased stem cells. Progesterone treatment also increases breast CSCs in established breast cancer cell lines. This is mediated in part through progesterone regulation of transcription factors, signal transduction pathways, and microRNAs. There is also emerging evidence that estrogens and androgens can regulate breast CSC numbers. The evolving concept that a breast CSC phenotype is dynamic and can be influenced by cell signaling and external cues emphasizes that steroid hormones could be crucial players in controlling CSC number and function. Here we review recent studies on steroid hormone regulation of breast CSCs, and discuss mechanisms by which this occurs.

Keywords

Progesterone Progesterone receptor Cancer stem cells Hormone replacement therapy Breast cancer Steroid hormone 

Abbreviations

AR

Androgen receptor

ALDH

Aldehyde dehydrogenase

CK5

Cytokeratin 5

CSC

Cancer stem cell

DHT

Dihydrotestosterone

DMBA

7,12-dimethylbenz(a)anthracene

EGFR

Epidermal growth factor receptor

ER

Estrogen receptor (alpha)

FACS

Fluorescent activated cell sorting

FGF

Fibroblast growth factor

HRT

Hormone replacement therapy

MaSC

Mammary stem cell

MMTV

Mouse mammary tumor virus

MPA

Medroxyprogesterone acetate

MUC1

Mucin 1

PR

Progesterone receptor

PRKO

Progesterone receptor knockout

RANK

Receptor activator of nuclear factor kappa-B

RANKL

receptor activator of nuclear factor kappa-B ligand

TNBC

triple negative breast cancer

Notes

Acknowledgments

This work was supported in part by grants NIH R01 CA140985 (CAS) and NIH 1F32CA177081 (JFS). The authors wish to apologize to those whose work was not referenced due to space limitations.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of PathologyUniversity of Colorado Anschutz Medical CampusAuroraUSA

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