Modulation of PPAR-Gamma Signaling in Prostatic Carcinogenesis
Abstract
The long term objective of this work is to elucidate metabolic pathways which can be used to reduce the need for radical surgery in patients at high risk for prostate cancer or with early stage disease. The hypothesis to be tested is that alterations to lipoxygenase (LOX) and cyclooxygenase (COX) activity in early prostate cancer represent distinct druggable pathways which can be treated in conjunction with the PPAR-gamma signaling pathway to slow or prevent the development and progression of prostate cancer. In the first year of funding, we have generated many of the viral vectors (PPAR-gamma siRNAs, COX and LOX shRNA and overexpression) needed to perform the experiments in the bulk of the proposal. We have completed the majority of the experiments proposed in specific aim 1 relating to the knockdown of PPAR-gamma in human prostatic epithelial cells and have confirmed that these cells behave as predicted using in vivo models. These experiments are currently undergoing the final stages of analysis. We have started generation of cells with altered COX and LOX expression for the experiments proposed in specific aim 2. Work for specific aim 3 has not yet begun. Major findings from the first year of work are that human prostatic epithelial cells, as expected, respond to loss of PPAR-gamma signaling in the same way as mouse cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2008
- Accession Number
- ADA501164
Entities
People
- Simon W. Hayward
Organizations
- Vanderbilt University Medical Center