Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1
Annual rept. 2 Jan 2007-1 Jan 2008
PITTSBURGH UNIV PA
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To gain better mechanistic insight of the role of Fifteen lipoxygenase-1 15-LO-1 in prostate cancer PCa, we recently developed a novel C57BL6 transgenic mouse called 15-LO-1 in the Mouse Prostate FLiMP. 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. In year 1, we have studied the effect of n-6 linoleic acid LA in diet on the onset of PIN in prostates of FLiMP mice and studies with n-3 Stearidonic acid SDA in diet is ongoing. We observed that, a wild type WT mice did not exhibit any prostate-specific phenotypic changes regardless of their diet, b FLiMP mice fed a diet high LA diet exhibited more aggressive PIN, with PIN-like changes observed in as early as 10 weeks compared to FLiMP mice fed a normal diet PIN observed by week 20, and c the severity of these mPIN-like changes in the LA-diet fed mice are similar to those seen at 35 weeks or later in the FLiMP group which were on normal diet. This preliminary observation suggests the bad effects of excessive n-6 LA diet consumption in the progression of PCa.
- Medicine and Medical Research