Investigation of the Molecular Regulation of Prostate Basal Cell Multipotency

The goal of my thesis was to discover how basal cell multipotency is is regulated in the adult, homeostatic prostate. During development, basal stem cells actively differentiate to produce mature basal, luminal and neuroendocrine cells. Some basal cells retain this ability in adulthood, however the stem cell activity is heavily downregulated. Most of this thesis focuses on understanding cellular mechanisms that are responsible for modulation of basal stem cell activity. Chapter 2 examines a potential inhibitory signal emanating from luminal cell contact. Chapter 3 follows by investigating how the canonical Wnt and androgen receptor (AR) signaling pathways interact to induce basal stem cell activity. The 4th chapter takes a brief look into the internal programing of adult basal stem cells. A better understanding of the regulatory processes that govern stem cell activity is necessary in order to understand the pathogenesis of malignancies that arise from the alterations of these processes. To this end, the final chapter of this thesis uses mouse models of prostate adenocarcinoma to investigate the effect of stromal AR activity on cancer progression