Modulation of PPAR-Gamma Signaling in Prostatic Carcinogenesis
Abstract
This project examines the relationship between PPAR-gamma and carcinogenesis. PPAR-GAMMA sits at a critical juncture in cellular differentiation and metabolism being involved in both differentiation and in the regulation of stress responses mediated through the cyclooxygenase (COX) and lipoxygenase (LOX) pathways of fatty acid metabolism. The basis for this project was the observation that in human prostate cancer there is an early loss of enzymes responsible for the production of the putative endogenous ligands for PPAR-GAMMA, presumed to result in a decrease in receptor function. We have found that loss of PPARGAMMA function can result in the generation of premalignant prostatic lesions in mice (Jiang et al 2010). We have also shown that there is an associated upregulation of COX pathways which would generate increases in prostaglandin production and oxidative stress, which could underlie such pathology. This project sets out to examine interactions between the PPARGAMMA, COX and LOX pathways and their role in carcinogenesis. We are using predominantly tissue recombination models involving human prostatic epithelial cells. The use of human cells is important in that there are significant differences between the fatty acid metabolic pathways between humans and mice. However we have also generated mouse epithelial cell lines from the transgenic animals and as a result have been able to use their accelerated aging and metabolism as compared to human cells to illustrate malignant transformation in a recombination model. These data provide a strong basis for future studies
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2010
- Accession Number
- ADA538566
Entities
People
- Simon W. Hayward
Organizations
- Vanderbilt University Medical Center