Molecular mechanisms underlying progesterone receptor action in breast cancer: Insights into cell proliferation and stem cell regulation

The ovarian steroid hormone progesterone and its nuclear receptor, the Progesterone Receptor (PR), play an essential role in the regulation of cell proliferation and differentiation in the mammary gland. In addition, experimental and clinical evidence demonstrate their critical role in controlling mammary gland tumorigenesis and breast cancer development. When bound to its ligand, the main action of PR is as a transcription factor, which regulates the expression of target genes networks. PR also activates signal transduction pathways through a rapid or non-genomic mechanism in breast cancer cells, an event that is fully integrated with its genomic effects. This review summarizes the molecular mechanisms of the ligand-activated PR actions that drive epithelial cell proliferation and the regulation of the stem cell population in the normal breast and in breast cancer.