Date of Award

December 2018

Degree Type

Thesis

Degree Name

Master of Science

Department

Biomedical Sciences

First Advisor

Jennifer Doll

Committee Members

Jennifer Doll, Elizabeth Liedhegner, Dean Nardelli

Keywords

Adipose, Liver, PEDF, Pigment Epithelium Derived Factor, Prostate

Abstract

Prostate cancer is the second most common form of cancer among males in the United States. An association has been established between aggressive prostate cancer and obesity. The obese microenvironment can promote tumor growth. The Serpinf1 gene encodes pigment epithelium-derived factor (PEDF), a tumor suppressor gene which has anti-angiogenesis and direct anti-tumor properties. Notably, expression of this protein is suppressed in prostate cancer cells. Our lab has previously demonstrated further suppression of PEDF expression within a prostate epithelial cell line and prostate cancer cell lines in vitro, when the cells were grown in an obese microenvironment. The experiments outlined in this study were conducted to determine if PEDF expression is suppressed in vivo, in prostate, liver, and periprostatic adipose tissue in an obese microenvironment. It was hypothesized that the PEDF levels would be lower in the prostate tissues and periprostatic adipose tissue, but higher in liver tissue in the obese microenvironments. In vivo experiments were conducted using two different obesity models, (A) wild-type C57BL/6 mice on a control diet (CD) or a high fat diet (HFD) and (B) wild-type and Ob/ob strains of C57BL/6 mice on a standard laboratory diet. All experimental diets began at 8 weeks of age and were carried out for 16 weeks. Prostate, liver, and adipose tissues were harvested when mice were 6 months old. Protein levels in tissue homogenates were analyzed with a Coomassie assay. Then, PEDF protein levels were quantified with an ELISA. In the majority of samples, no significant difference in PEDF levels was found when comparing the HFD or ob/ob mice to their respective control group. One difference was observed within the anterior prostate lobe in the ob/ob mice. This experiment also suggested that there are higher levels of PEDF in the ventral prostate lobe in the WT control mice when compared to the anterior and dorsolateral prostate lobes. These are the first reported data of PEDF levels in both the prostate and periprostatic adipose tissue in mice. While these data, overall, did not support the hypothesis, due to large variances in PEDF levels, further studies are needed to confirm that an obese microenvironment does indeed have no effect on PEDF levels in prostate, liver, and adipose tissue in vivo.

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