Date of Award

August 2015

Degree Type

Thesis

Degree Name

Master of Science

Department

Biomedical Sciences

First Advisor

Jennifer A. Doll

Committee Members

Dean Nardelli, Janis Eells

Keywords

Obesity, Oxidative Stress, Pigment Epithelium Derived Factor, Prostate Cancer

Abstract

Aggressive prostate cancer (PCa) is positively correlated with obesity and a high fat diet, suggesting that dysregulated lipid metabolism promotes PCa progression. Pigment epithelium-derived factor (PEDF) regulates angiogenesis, lipid metabolism, and has antioxidant function in other cell types. In the prostate, PEDF inhibits angiogenesis, and its expression is decreased in PCa. However, PEDF’s role in regulating lipid metabolism and oxidative stress levels has not been investigated, and, as such, was the goal of the present study. Oxidative stress levels were evaluated in vivo and ex vivo in prostate and adipose tissues from wildtype (C56Bl/6J) and PEDF knockout (KO) mice. In vitro, human normal prostate or PCa cell lines were treated with PEDF with or without oleic acid (lipid overload model). Reactive oxygen and reactive nitrogen species (ROS/RNS) and antioxidant enzyme levels (GPx-3 and mSOD) were quantified using an ROS/RNS detection assay and Western blot, respectively. Loss of PEDF in adipose tissue increased ROS/RNS, indicating elevated oxidative stress. PEDF loss also decreased GPx-3 and mSOD levels in the adipose tissue. However, these results were not seen in the prostate or in PCa cells. While these data do support the hypothesis that PEDF has some antioxidant function in adipose tissue, further studies are needed to elucidate this role.

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