Prostaglandin E2 production in ovarian cancer cell lines is regulated by cyclooxygenase-1, not cyclooxygenase-2.
The significance of cyclooxygenase-2 (COX-2) expression in ovarian cancer has been discussed. In this study, we found increased expression of COX-1 mRNA and protein in three out of 10 ovarian cancer cell lines. Prostaglandin E 2 (PGE2) production was elevated in these three cell lines, but not in other seven cell lines. COX-2 protein was not detected in any of the cell lines. Cytosolic prostaglandin E synthase (cPGES) mRNA and protein were detected in all 10 cell lines. Membrane-associated PGES-1 (mPGES-1) was detected in some of the ovarian cell lines, but its presence did not correspond with PGE2 production. In contrast, mPGES-2 mRNA and protein were detected in all 10 cell lines. A nonselective COX inhibitor (indometacin) and a selective COX-1 inhibitor (SC-560) strongly inhibited PGE2 production by the three cell lines, while selective COX-2 inhibitors (NS-398 and rofecoxib) did not inhibit PGE2 production. In addition, increased expression of COX-1, not COX-2 protein was observed in the mass of ovarian cancer tissues from 22 patients when compared with that in normal tissue. These findings suggest that COX-1 might be a major enzyme regulating PGE2 production in ovarian cancer cells.
Kino
Yuko
Y
Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki-shi, Kanagawa 216-8512, Japan.
Kojima
Fumiaki
F
Kiguchi
Kazushige
K
Igarashi
Rie
R
Ishizuka
Bunpei
B
Kawai
Shinichi
S
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015232:Dinoprostone / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012333:RNA, Messenger; D015232:Dinoprostone