Progenitor Cells for the Prostate Epithelium: Roles in Development, Regeneration, and Cancer

Abstract

The identification of stem cell/progenitor populations represents a critical step for deducing the putative cell type(s) of origin for epithelial cancers and may provide important therapeutic insights. In the case of the prostate gland, recent studies have made significant progress in the identification of candidate stem cell populations, but they have left unresolved key questions about their tissue localization and functional properties. In our work, we have used genetic lineage marking in vivo to demonstrate that a rare epithelial cell population marked by expression of the Nkx3.1 homeobox gene in the androgen-deprived prostate contains bipotential progenitor cells that are capable of self-renewal. Inducible targeting of the Pten tumor suppressor in these castrate-resistant Nkx3.1-expressing cells demonstrates that this stem/progenitor population is also a potent cell of origin for prostate cancer in mouse models. These findings may help to explain several intriguing features of prostate cancer and its phenotypic progression.