Heightened expression of cyclooxygenase-2 and peroxisome proliferator-activated receptor-delta in human endometrial adenocarcinoma

Epidemiological studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) significantly reduce the risk and mortality from colorectal cancer , in part by inhibiting prostaglandin (PG) synthesis. Cyclooxygenase (COX), the rate-limiting enzyme in PG biosynthesis, exists in two isoforms, COX-1 and COX-2, Genetic and pharmacological evidences suggest that COX-2 is inv olved in the development of colorectal cancer. We have previously shown tha t COX-2-derived prostacyclin participates in blastocyst implantation throug h activation of peroxisome proliferator activated receptor delta (PPAR delt a), a member of the nuclear hormone receptor family. Furthermore, our recen t studies suggest that a similar pathway is operative during colorectal car cinogenesis. These observations prompted us to examine whether the COX-2-PP AR delta signaling pathway is also involved during development of uterine a denocarcinoma. Here we describe for the first time the heightened expressio n of COX-2 and PPAR delta, but not COX-1, in uterine endometrial adenocarci noma.