Project Description
Prostate cancer (PCa) is the second leading cause of cancer death in men. Risk factors include older age, a high fat diet, and obesity. Obesity correlates with more aggressive PCa and higher mortality. Moreover, high serum glucose levels correlate with a higher risk of PCa recurrence. However, the mechanism of high glucose’s effect on PCa is not well elucidated. The prostate’s function is to secrete seminal fluid, and citrate is a key component of this fluid, which is derived from the Tricarboxylic Acid Cycle (TAC) through zinc-mediated inhibition of m-aconitase, the enzyme that converts citrate to isocitrate. This results in the prostate having very high zinc tissue levels, which then decrease in PCa. Zinc has been shown to have some anti-cancer activities, but there is some conflicting data. Our studies are examining zinc regulation within the normal prostate and PCa. We are focusing on the zinc efflux transporters (ZnTs), including ZnT1 and ZnT4. We are examining changes in expression levels and membrane localization levels in response to varying glucose concentrations and plan to investigate how glucose mediates changes in these levels.