Induction of prostaglandin G/H synthase-2 in a canine model of spontaneous prostatic adenocarcinoma.

BACKGROUND Prostate cancer is the most frequently occurring cancer in men in the United States, with an estimated 179 300 new cases in 1999. The induction of prostaglandin G/H synthase (PGHS), a key rate-limiting enzyme in prostaglandin biosynthesis, has been implicated in various cancers, most notably in colorectal cancers; however, the induction of PGHS expression in prostate cancer in vivo has not been reported for any species. The dog is the only nonhuman species that frequently develops spontaneous cancer of the prostate with increasing age, and the objective of this study was to determine whether PGHS isoenzymes were expressed in canine prostatic adenocarcinomas. METHODS Four normal canine prostatic tissues and 24 canine prostatic adenocarcinomas were studied by means of immunohistochemistry and immunoblot analysis, using polyclonal antibodies specific for each of the two PGHS isoenzymes, PGHS-1 and PGHS-2. All P values were obtained by use of two-sided Fisher's exact tests. RESULTS PGHS-1 immunostaining was localized to stromal fibroblasts and vascular endothelium in normal and cancerous prostates. PGHS-2 was not detected in normal prostates, but it was expressed by epithelial tumor cells in 18 (75%) of the 24 adenocarcinomas (P =.01). Immunoblot analysis confirmed the presence of PGHS-1 (69 000 molecular weight) in normal and cancerous tissues and the expression of PGHS-2 (72 000- to 74 000-molecular-weight doublet) only in prostatic adenocarcinomas. CONCLUSION To our knowledge, these results demonstrate for the first time that PGHS-2 is induced in the majority of canine spontaneous prostatic adenocarcinomas and suggest that its expression may be involved in prostate cancer.