Impact of Progesterone on Stem/Progenitor Cells in the Human Breast

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Abstract

The epithelium of the human breast is made up of a branching ductal-lobular system, which is lined by a single layer of luminal cells surrounded by a contractile basal cell layer. The co-ordinated development of stem/progenitor cells into these luminal and basal cells is fundamentally important for breast morphogenesis. The ovarian steroid hormone, progesterone, is critical in driving proliferation and normal breast development, yet progesterone analogues have also been shown to be a major driver of breast cancer risk. Studies in recent years have revealed an important role for progesterone in stimulating the mammary stem cell compartment in the mouse mammary gland, and growing evidence supports the notion that progesterone also stimulates progenitor cells in both the normal human breast and in breast cancer cells. As changes in cell type composition are one of the hallmark features of breast cancer progression, these observations have critical implications in discerning the mechanisms of how progesterone increases breast cancer risk. This review summarises recent work regarding the impact of progesterone action on the stem/progenitor cell compartment of the human breast.

Keywords

Progesterone Breast cancer Human breast Progenitor Stem cell 

Abbreviations

ALDH

Aldehyde dehydrogenase

CK5

Cytokeratin-5

CK8

Cytokeratin-8

CK14

Cytokeratin-14

CSC

Cancer stem cell

DLL-1

Delta-like 1

DLL-3

Delta-like 3

E

Estrogen

ER

Estrogen receptor

GH

Growth hormone

GHR

Growth hormone receptor

IF

Immunofluorescence

HRT

Hormone replacement therapy

LRECs

Label-retaining epithelial cells

miRNA

microRNA

MPA

Medroxyprogesterone acetate

P

Progesterone

PR

Progesterone receptor

RANKL

Receptor activator of nuclear factor-kB ligand

SMA

Smooth muscle actin

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Notes

Acknowledgments

HNH is supported by a Postdoctoral Fellowship co-funded by the Cure Cancer Australia Foundation and the National Breast Cancer Foundation. CLC is a research fellow of the National Health and Medical Research Council of Australia.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Centre for Cancer Research, Westmead Millennium InstituteUniversity of Sydney Medical SchoolWestmeadAustralia

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