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

Breast Cancer Res Treat. 2014 Feb;143(3):423-33. doi: 10.1007/s10549-013-2817-2. Epub 2014 Jan 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast / drug effects*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Cell Lineage
  • Cell Proliferation / drug effects*
  • Estradiol / administration & dosage
  • Estradiol / genetics
  • Female
  • Humans
  • Hyaluronan Receptors / genetics
  • Neoplastic Stem Cells / drug effects
  • Neprilysin / genetics
  • Progesterone / administration & dosage*
  • Progesterone / genetics
  • Receptors, Estrogen / metabolism
  • Stem Cells / drug effects

Substances

  • Hyaluronan Receptors
  • Receptors, Estrogen
  • Progesterone
  • Estradiol
  • Neprilysin