Progesterone stimulates progenitor cells in normal human breast and breast cancer cells

• DOI: 10.1007/s10549-013-2817-2
• Publication Date: 2014-01-06T18:47:37Z
• Authors: Heidi N. Hilton; N. Santucci; A. Silvestri; S. Kantimm; L. I. Huschtscha; J. D. Graham; C. L. Clarke
• Keywords: 0301 basic medicine; Estradiol; Stem Cells; Breast Neoplasms; Cell Differentiation; 3. Good health; 03 medical and health sciences; Hyaluronan Receptors; Receptors, Estrogen; Cell Line, Tumor; Neoplastic Stem Cells; Humans; Cell Lineage; Female; Neprilysin; Breast; Progesterone; Cell Proliferation

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.