Accession Number : ADA525561


Title :   Modulation of PPAR-Gamma Signaling in Prostatic Carcinogenesis


Descriptive Note : Annual rept. 1 Sep 2008-1 Sep 2009


Corporate Author : VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN


Personal Author(s) : Hayward, Simon W


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/a525561.pdf


Report Date : Sep 2009


Pagination or Media Count : 22


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 second year of funding, we have generated and applied the various viral vectors (PPAR-gamma siRNAs, COX and LOX shRNA and overexpression) and have generated many of the tissue recombinants needed to perform the proposed experiments. We have completed the majority of the experiments proposed in specific aim 1 and are writing this work up for publication. As in the mouse model loss of PPAR-gamma function in human epithelium leads to a PIN phenotype which can be promoted to cancer with additional genetic insults. We have generated cells and recombinants with altered COX and LOX expression for the experiments proposed in specific aim 2 which are now ongoing. Work for specific aim 3 is just starting. The second year of work has demonstrated that the combination of PPAR-gamma loss with other common genetic insults can cause progression of a PIN phenotype.


Descriptors :   *PROSTATE CANCER , METABOLISM , ONCOGENESIS , ENZYMES , CELLS(BIOLOGY)


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE