Though much progress has been made during the past two decades, the prostate epithelial lineage hierarchy is still not completely characterized. There are three types of epithelial cells in the prostate. Luminal cells surround the lumen and carry out the secretory function. Basal cells are aligned between the luminal cells and the basement membrane. Neuroendocrine cells are rare and are less well studied because of a lack of experimental tools. Prostate tissues are capable of undergoing alternate regression and regeneration in response to fluctuating serum testosterone levels. This observation implies the existence of stem cells that possess extensive regenerative capacity. During the past few years, we and several other groups have demonstrated that prostate basal cells and luminal cells are independently sustained in adult rodents, suggesting the existence of respective stem/progenitors in these two lineages. While the identity of stem cells in the basal cell lineage has been abundantly characterized, the identity of stem cells in the luminal cell lineage remains undefined. The goal of this renewal application is to employ genetically engineered mouse models to define the identity of the luminal progenitors using a lineage tracing approach and investigate the molecular mechanisms that regulate the maintenance and differentiation of luminal progenitors diseases.
Deregulation of prostate stem cell homeostasis plays a role in initiation of the prostate-related disease including benign prostatic hyperplasia (BPH). Some intrinsic properties of the prostate stem cells such as extensive regenerative potential and androgen-independent survival may contribute to the pathological features of BPH such as progressive epithelial proliferation and finasteride irresponsiveness etc. Understanding the identity of prostate stem cells and critical signaling that regulate their maintenance and differentiation will inspire novel therapeutic strategies for these prostate related diseases.
