The Role of Central Metabolism in Prostrate Cancer Progression
Abstract
Work from our laboratories and others suggests that the metabolites of dietary omega~ 3 and ~6 polyunsaturated fatty acids (PUFAs) directly affect PCa and the ability to do so depends on intake and metabolic enzyme expression. Omega~3 and ~6 PUFAs compete as substrates for cyclooxygenase~2 and 15~lipoxygenase~1, both elevated in PCa; these enzymes convertomega~ 3 PUFAs to anti~tumorigenic metabolites and omega~6 to pro~tumorigenic ones. PCa cells also have elevated fatty acid synthase (FASN). FASN regulates the expression of a myriad of genes, including the PUFA metabolic enzymes delta~5 and ~6 desaturase and phospholipases that liberate arachidonic acid, which together may affect the pool of PUFAs. In addition, omega~3 inhibits FASN, inducing apoptosis in PCa cell lines. We will identify the proteins and modifications involved in PCa specific dysregulation of fatty acid metabolic networks to identify and validate diagnostic and prognostic biomarkers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2010
- Accession Number
- ADA541939
Entities
People
- Uddhav P. Kelavkar
Organizations
- University of Pittsburgh