Heightened Expression of Cyclooxygenase-2 and Peroxisome Proliferator-Activated Receptor-δ 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 involved in the development of colorectal cancer. We have previously shown that COX-2-derived prostacyclin participates in blastocyst implantation through activation of peroxisome proliferator activated receptor δ (PPARδ), a member of the nuclear hormone receptor family. Furthermore, our recent studies suggest that a similar pathway is operative during colorectal carcinogenesis. These observations prompted us to examine whether the COX-2-PPARδ signaling pathway is also involved during development of uterine adenocarcinoma. Here we describe for the first time the heightened expression of COX-2 and PPARδ, but not COX-1, in uterine endometrial adenocarcinoma.