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 evidence 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 delta (PPARdelta), 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-PPARdelta signaling pathway is also involved during development of uterine adenocarcinoma. Here we describe for the first time the heightened expression of COX-2 and PPARdelta, but not COX-1, in uterine endometrial adenocarcinoma.
Tong
B J
BJ
Department of Obstetrics and Gynecology, Ralph L. Smith Research Center, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Tan
J
J
Tajeda
L
L
Das
S K
SK
Chapman
J A
JA
DuBois
R N
RN
Dey
S K
SK
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D015152:Blotting, Northern; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases