Epithelial cell lineage specification during prostate organogenesis and regeneration (210.4)

Abstract

The prostate gland is a particularly interesting system for the investigation of cell lineage specification given the central role of androgen signaling in all aspects of its development and function, as well as its ability to undergo serial regression and regeneration in response to androgen deprivation and restoration. In our previous studies, we have shown that a known regulator of prostate epithelial differentiation, the homeobox gene Nkx3.1, marks a luminal stem cell population that functions during prostate regeneration and is an efficient target for oncogenic transformation in prostate cancer. Genetic lineage‐tracing studies demonstrated that these rare cells which express Nkx3.1 in the absence of testicular androgens (castration‐resistant Nkx3.1‐expressing cells, CARNs) are bipotential and can self‐renew in vivo, and can serve as a cell of origin for prostate cancer. In parallel studies, we have utilized lineage‐tracing and transplantation approaches to explore the stem/progenitor properties of prostate basal cells during regeneration and tissue homeostasis, and observed an unexpected plasticity of basal cells in these assays. We will present our recent findings on prostate lineage specification and discuss their implications with respect to the relationship between epithelial progenitor populations and prostate cancer initiation.