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J Mammary Gland Biol Neoplasia. 2015 Jun;20(1-2):9-25. doi: 10.1007/s10911-015-9337-0. Epub 2015 Jul 19.

Form and function: how estrogen and progesterone regulate the mammary epithelial hierarchy.

Arendt LM1,2,3,4, Kuperwasser C5,6,7,8.

Author information

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.
2
Molecular Oncology Research Institute, Tufts Medical Center, 800 Washington St, Boston, MA, 02111, USA.
3
Raymond and Beverly Sackler Laboratory for the Convergence of Biomedical, Physical and Engineering Sciences, Boston, MA, 02111, USA.
4
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Dr, Madison, WI, 53706, USA.
5
Developmental, Molecular, and Chemical Biology Department, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA, 02111, USA. Charlotte.Kuperwasser@tufts.edu.
6
Molecular Oncology Research Institute, Tufts Medical Center, 800 Washington St, Boston, MA, 02111, USA. Charlotte.Kuperwasser@tufts.edu.
7
Raymond and Beverly Sackler Laboratory for the Convergence of Biomedical, Physical and Engineering Sciences, Boston, MA, 02111, USA. Charlotte.Kuperwasser@tufts.edu.
8
Developmental, Molecular, and Chemical Biology Department, Tufts University School of Medicine, 800 Washington St, Box 5609, Boston, MA, 02111, USA. Charlotte.Kuperwasser@tufts.edu.

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.

KEYWORDS:

Breast; Estrogen; Mammary epithelial cells; Progenitor cells; Progesterone

PMID:
26188694
PMCID:
PMC4596764
DOI:
10.1007/s10911-015-9337-0
[Indexed for MEDLINE]
Free PMC Article

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