Date of Award

2019

Document Type

Thesis

Degree Name

Master of Biomedical Science

Department

Pathology and Laboratory Medicine

College

College of Graduate Studies

First Advisor

David P. Turner

Second Advisor

Victoria Findlay

Third Advisor

Michael Lilly

Fourth Advisor

Michael Ostrowski

Fifth Advisor

Laura Spruill

Abstract

Prostate cancer is the second most common cancer in men and one of the leading causes of cancer deaths among men in America. Interestingly, it has been shown that immigration and the adaption of a Western-Diet can significantly increase the risk of prostate cancer development in men, suggesting diet may play a key role in prostate cancer development. Advanced glycation end products (AGEs) are reactive metabolites that are produced during normal metabolism and accumulate in our tissues and organs as we get older. AGE content in the Western-Diet has significantly increased over the years leading to an increase of AGE consumption through the foods we eat, thus leading to an accumulation in our tissue and organs. The accumulation of AGEs can lead to pathogenic effects such as oxidative stress, inflammation, known factors which can contribute to the development and progression of prostate cancer. This study examines the effects of a high AGE diet on prostate tumor growth in a syngeneic mouse model. Mice were fed a constant control (regular) diet, a constant high AGE diet, a diet switched from regular to high AGE, or a diet switched from high AGE to regular. Each mouse group was fed their respective diet from weaning (3 weeks), followed by injection of MYC-CaP cells into the flank at 6 weeks of age, and monitored until 12 weeks of age. Diet switch groups were switched at point of injection to the opposite diet. From point of injection, tumor growth was measured. At the experimental endpoint, tumors were excised and analyzed through immunofluorescence (IF), hematoxylin and eosin (H&E) staining, RNA sequencing, and Real Time PCR analysis. The high AGE diet revealed a threefold increase in tumor volume when compared to the regular diet, however when diet was switched tumor growth was not fully inhibited. Histology revealed changes in the morphology of the tumors from regular to high AGE diets showing an increase in cell density. RNA sequencing along with Real Time PCR showed genes and pathways associated with prostate cancer development to be altered by a high AGE diet to promote cancer development. In summary, we observed a significant change in the cellular and molecular components of the prostate tumors when exposed to a diet high in AGEs, possibly leading to the link between diet and increased prostate cancer development.

Rights

All rights reserved. Copyright is held by the author.

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