Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1
Abstract
Fifteen lipoxygenase-1 (15-LO-1) in the Mouse Prostate (FLiMP)- A novel mouse model to study impact of omega diets on prostate cancer progression: To gain better mechanistic insight of the role of 15-LO-1 in prostate cancer (PCa), we recently developed a novel C57BL/6 transgenic mouse called FLiMP [1]. These mice, which conditionally express prostatic human 15-LO-1, display mouse prostatic intraepithelial neoplasia (mPIN) by week 20, but do not progress to cancer when on normal diet. Therefore, FLiMP mice provide an excellent model to study the experimental paradigm of PCa initiation, highlighting their usefulness in evaluating early "proactive" intervention strategies in PCa. Our proposed studies are predicated on the hypothesis that dietary prevention is an effective means of eradicating PCa, and that FLiMP mice provide a valuable pre-clinical model for chemoprevention studies. Diets rich in either omega (w)-3 or w-6 polyunsaturated fatty acids (PUFAs) directly impact PCa tumor growth. Furthermore, the FLiMP mice, which overexpress human 15-LO-1, faithfully recapitulate the early stages of human PCa progression. These observations support the potential value of w-3 fatty acid SDA as a chemopreventative agent and the need for further studies. Thus, the FLiMP mouse model has the strength of being a genetically defined, immune-competent tool to address the w-6 and w-3 experimental paradigm.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2009
- Accession Number
- ADA502327
Entities
People
- Uddhav P. Kelavkar
Organizations
- University of Pittsburgh