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Form and Function: how Estrogen and Progesterone Regulate the Mammary Epithelial Hierarchy

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

The mammary gland undergoes dramatic post-natal growth beginning at puberty, followed by full development occurring during pregnancy and lactation. Following lactation, the alveoli undergo apoptosis, and the mammary gland reverses back to resemble the nonparous gland. This process of growth and regression occurs for multiple pregnancies, suggesting the presence of a hierarchy of stem and progenitor cells that are able to regenerate specialized populations of mammary epithelial cells. Expansion of epithelial cell populations in the mammary gland is regulated by ovarian steroids, in particular estrogen acting through its receptor estrogen receptor alpha (ERα) and progesterone signaling through progesterone receptor (PR). A diverse number of stem and progenitor cells have been identified based on expression of cell surface markers and functional assays. Here we review the current understanding of how estrogen and progesterone act together and separately to regulate stem and progenitor cells within the human and mouse mammary tissues. Better understanding of the hierarchal organization of epithelial cell populations in the mammary gland and how the hormonal milieu affects its regulation may provide important insights into the origins of different subtypes of breast cancer.

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Abbreviations

ALDH:

Aldehyde dehydrogenase

CK:

Cytokeratin

EGF:

Epidermal growth factor

Elf5:

E74-like factor

ERα:

Estrogen receptor alpha

FACS:

Fluorescence-activated cell sorting

GH:

Growth hormone

H2BGFP:

Histone H2B fused to eGFP

ME:

Myoepithelial

MMTV:

Mouse mammary tumor virus

MRU:

Mammary repopulating units

PI-MEC:

Pregnancy-induced mammary epithelial cells

PR:

Progesterone receptor

sca-1:

Stem cell antigen-1

SMA:

Smooth muscle actin

TDLU:

Terminal ductal lobule unit

TGFα:

Transforming growth factor alpha

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Acknowledgments

The authors would like to thank Drs. Jerrica Breindel and Ania Wronski and John Hinds for a critical review of the manuscript. NIH/NICHD HD073035, NIH/NICHD CA170851 and The Breast Cancer Research Foundation.

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Authors and Affiliations

  1. Developmental, Molecular, and Chemical Biology Department, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA, 02111, USA

    Lisa M. Arendt & Charlotte Kuperwasser

  2. Molecular Oncology Research Institute, Tufts Medical Center, 800 Washington St, Boston, MA, 02111, USA

    Lisa M. Arendt & Charlotte Kuperwasser

  3. Raymond and Beverly Sackler Laboratory for the Convergence of Biomedical, Physical and Engineering Sciences, Boston, MA, 02111, USA

    Lisa M. Arendt & Charlotte Kuperwasser

  4. Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Dr, Madison, WI, 53706, USA

    Lisa M. Arendt

  5. Developmental, Molecular, and Chemical Biology Department, Tufts University School of Medicine, 800 Washington St, Box 5609, Boston, MA, 02111, USA

    Charlotte Kuperwasser

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Arendt, L.M., Kuperwasser, C. Form and Function: how Estrogen and Progesterone Regulate the Mammary Epithelial Hierarchy. J Mammary Gland Biol Neoplasia 20, 9–25 (2015). https://doi.org/10.1007/s10911-015-9337-0

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