Impact of inflammation on prostate stem cells

Hsing-Hui Wang, Purdue University

Abstract

Prostate inflammation has been associated with various prostatic pathogenesis, including benign prostate hyperplasia and prostate cancer, based on cumulating histological and epidemiological reports. Cellular and molecular mechanisms by which prostate inflammation impacts on prostatic pathogenesis remain elusive due to the limited accessibility of clinical prostate inflammation specimen, as well as the lack of a representative prostate inflammation animal models. The overall dissertation is to validate the impact of autoimmune mediated prostate inflammation on adult prostate stem cells (PSC), by utilizing an established T-cell mediated autoimmune prostate inflammation mouse model, prostate ovalbumin expressing transgenic mice -3 (POET-3). The central hypothesis in this dissertation is that prostate inflammation promotes proliferation and differentiation of PSC, ultimately resulting in prostate epithelial hyperplasia. In the presence study, cellular characterization of PSC and prostate progenitor cells in vitro and in vivo show that induction of inflammation results in an increased amount of prostate progenitor population, while the self-renewal ability of PSC remains. Data also show that inflammation regulated PSC is able to clonally generate larger, better basal-to-luminal stratified and more tubule-like spheroids than normal PSC in a non-inflammatory and androgen free environment, indicating that the autonomous characteristics of PSC has been altered by acute induction of inflammation. Significant nuclear localized androgen receptor (AR) expression in inflammation regulated PSC derived prostate spheroids suggests that testicular androgen independent AR activity is one potential molecular mechanism in the process of PSC expansion. Elevated expression of an AR responsive gene, Tmprss2, in inflamed progenitor cells, confirms the existence of AR signaling in prostate progenitor cell stage. Chemically and genetically abrogation of AR function significantly deprives PSC clonal propagation and the basal-to-luminal lineage hierarchy in sphere formation. Data presented here suggest activation of AR as a molecular mechanism of prostate inflammation driven PSC expansion.^

Degree

Ph.D.

Advisors

Timothy L. Ratliff, Purdue University.

Subject Area

Molecular biology|Cellular biology

Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server
.

Share

COinS