Induction of prostaglandin G/H synthase-2 in a canine model of spontaneousprostatic adenocarcinoma

Background: Prostate cancer is the most frequently occurring cancer in men in the United States, with an estimated 179300 new cases in 1999, The induc tion of prostaglandin G/H synthase (PGHS), a key rate-limiting enzyme in pr ostaglandin biosynthesis, has been implicated in various cancers, most nota bly in colorectal cancers; however, the induction of PGHS expression in pro state cancer in vivo has not been reported for any species. The dog is the only nonhuman species that frequently develops spontaneous cancer of the pr ostate with increasing age, and the objective of this study was to determin e whether PGHS isoenzymes were expressed in canine prostatic adenocarcinoma s. Methods: Four normal canine prostatic tissues and 24 canine prostatic ad enocarcinomas were studied by means of immunohistochemistry and immunoblot analysis, using polyclonal antibodies specific for each of the two PGHS iso enzymes, 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 stro mal fibroblasts and vascular endothelium in normal and cancerous prostates, PGHS-2 was not detected in normal prostates, but it was expressed by epith elial tumor cells in 18 (75%) of the 24 adenocarcinomas (P = .01). Immunobl ot analysis confirmed the presence of PGHS-1 (69000 molecular weight) in no rmal and cancerous tissues and the expression of PGHS-2 (72000- to 74000-mo lecular-weight doublet) only in prostatic adenocarcinomas. Conclusion: To o ur knowledge, these results demonstrate for the first time that PGHS-2 is i nduced in the majority of canine spontaneous prostatic adenocarcinomas and suggest that its expression may be involved in prostate cancer.