Arachidonate 15-Lipoxygenase 2 as an Endogenous Inhibitor of Prostate Cancer Development
Abstract
Studies from our lab and others' have implicated one class of lipid molecules, arachidonic acid (AA) lipoxygenases (LOXs) and their products, in prostate tumorigenesis. Our recent work has demonstrated that: 1) 15-L%OX2, which metabolizes AA to generate 15(S)-HErE, is the major LOX expressed in adult prOstate epithelial cells but down-regulated or lo Pca in vitro as well as in' vivo; 2)% 15-LOX2 expression is inversely correlated wfth%tii%%patholog%al grade and Gleason score of PCa pThinenfs; 3) 15-LOX2 is a negative cell-cycle regulator in normal human prostate (NHP) epithelial cells; 4) 15(S)-HErE inhibits PCa cell migration and invasion; 5) Re-expression of 15-LOX2, or its splice variant iS-LOX2sv-b, inhibits PCa cell proliferation in vitro and tumor development in vivo. These observations suggest that 15-LOX2 may represent a fi%nctional prostate tumor suppressor, whose loss of expression contributes to PCa development. We proposed two Specific Aims: 1) to test the hypothesis that 15-LOX2 inhibits PCa development in an onhotopic implantation model using an inducible 15-LOX2 expression system; and 2) to test the hypothesis that 15-LOX2 inhibits PCa development in newly developed prostate-specific transgenic animal models. By now we have finished most experiments in Specific Aim 1, with a manuscript published in JBC. We are currently focusing on Specific Aim 2.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2004
- Accession Number
- ADA425644
Entities
People
- Dean Tang
Organizations
- The University of Texas MD Anderson Cancer Center