Erschienen in:
01.02.2014 | Preclinical study
Progesterone stimulates progenitor cells in normal human breast and breast cancer cells
verfasst von:
Heidi N. Hilton, N. Santucci, A. Silvestri, S. Kantimm, L. I. Huschtscha, J. D. Graham, C. L. Clarke
Erschienen in:
Breast Cancer Research and Treatment
|
Ausgabe 3/2014
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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 hormones, progesterone (P) and 17β-estradiol, are critical in driving this normal breast development, yet ovarian activity has also been shown to be a major driver of breast cancer risk. We previously demonstrated that P treatment increases proliferation and augments the number of progenitor-like cells, and that the progesterone receptor (PR) is also expressed in the bipotent progenitor-enriched subfraction. Here we demonstrate that PR is expressed in a subset of CD10+ basal cells and that P stimulates this CD10+ cell compartment, which is enriched for bipotent progenitor activity. In addition, we have shown that P stimulates progenitor cells in human breast cancer cell lines and expands the cancer stem cell population via increasing the stem-like CD44+ population. As changes in cell type composition are one of the hallmark features of breast cancer progression, the demonstration that progenitor cells are stimulated by P in both normal breast and in breast cancer cells has critical implications in discerning the mechanisms of how P increases breast cancer risk.