Progesterone and estrogen receptors segregate into different cell subpopulations in the normal human breast

H N Hilton; J D Graham; S Kantimm; N Santucci; D Cloosterman; L I Huschtscha; P A Mote; C L Clarke

doi:10.1016/j.mce.2012.04.010

Progesterone and estrogen receptors segregate into different cell subpopulations in the normal human breast

Mol Cell Endocrinol. 2012 Sep 25;361(1-2):191-201. doi: 10.1016/j.mce.2012.04.010. Epub 2012 May 2.

Authors

H N Hilton¹, J D Graham, S Kantimm, N Santucci, D Cloosterman, L I Huschtscha, P A Mote, C L Clarke

Affiliation

¹ Westmead Institute for Cancer Research, Sydney Medical School-Westmead, University of Sydney at Westmead Millennium Institute, Westmead, New South Wales 2145, Australia. heidi.hilton@sydney.edu.au

PMID: 22580007
DOI: 10.1016/j.mce.2012.04.010

Abstract

Progesterone is critical in normal breast development and its synthetic derivatives are emerging as major drivers of breast cancer risk. The recent demonstration that progesterone regulates the stem cell compartment in the murine mammary gland, despite the absence of progesterone receptor (PR) in mammary stem cells, highlights the fact that PR distribution in progenitor cell subsets in the human breast remains to be conclusively shown. By utilising two independent cell sorting strategies to fractionate cells into distinct subpopulations enriched for different cell lineage characteristics, we have demonstrated a consistent enrichment of PR transcripts, relative to estrogen receptor transcripts, in the bipotent progenitor subfraction in the normal human breast. We have also shown co-expression of both steroid hormone receptors with basal markers in a subset of human breast cells, and finally we have demonstrated that PR+ bipotent progenitor cells are estrogen-insensitive, and that estrogen regulates PR in mature luminal cells only.

Publication types

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

MeSH terms

Adult
Animals
Antigens, Neoplasm / metabolism
Biomarkers / metabolism
Breast / cytology*
Breast / metabolism*
Cell Adhesion Molecules / metabolism
Cell Differentiation / drug effects
Cell Separation
Cells, Cultured
Epithelial Cell Adhesion Molecule
Epithelial Cells / cytology
Epithelial Cells / drug effects
Epithelial Cells / metabolism
Estrogens / pharmacology
Female
Gene Expression Profiling
Gene Expression Regulation / drug effects
Humans
Integrin alpha6 / metabolism
Keratin-14 / metabolism
Mice
Middle Aged
Models, Biological
NIH 3T3 Cells
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptors, Estrogen / genetics
Receptors, Estrogen / metabolism*
Receptors, Progesterone / genetics
Receptors, Progesterone / metabolism*
Stem Cells / cytology
Stem Cells / drug effects
Stem Cells / metabolism
Young Adult

Substances

Antigens, Neoplasm
Biomarkers
Cell Adhesion Molecules
EPCAM protein, human
Epithelial Cell Adhesion Molecule
Estrogens
Integrin alpha6
Keratin-14
RNA, Messenger
Receptors, Estrogen
Receptors, Progesterone