Abstract
Gastrointestinal carcinomas synthesize elevated levels of prostaglandin E2 (PGE2), which has been mechanistically linked to carcinogenesis. Recently, microsomal prostaglandin E synthase-1 (mPGES-1) was cloned, which seems to be inducible and linked to cyclooxygenase-2 (Cox-2) in the biosynthesis of PGE2. We examined expression of mPGES-1 in intestinal type gastric adenocarcinomas and in gastric cancer cell lines. The transcript for mPGES-1 was elevated in 57% (4/7) of gastric carcinomas as detected by Northern blot analysis. Moderate to strong mPGES-1 immunoreactivity was observed in 56% (5/9) of the carcinomas as detected by immunohistochemistry. Furthermore, mPGES-1 mRNA, protein and microsomal PGES activity were detected in gastric adenocarcinoma cell lines that originated from intestinal type tumors (MKN-7 and MKN-28). In contrast to Cox-2, however, expression of MPGES-1 mRNA or protein were not induced by phorbol 12-myristate 13-acetate (PMA) or interleukin-1β (IL-1β) in any of the gastric cancer cell lines tested (MKN-1, -7, -28, -45 and -74). Two gastric cancer cell lines (MKN-45 and MKN-74) did not express mPGES-1 and lacked microsomal PGES activity, but were still able to synthesize PGE2. Because all gastric cell lines expressed cPGES as detected by immunoblotting, it is possible that Cox-2 can interact with cPGES or with some other yet unidentified PGES in gastric cancer cells. Furthermore, our data show that regulatory mechanisms that drive expression of mPGES-1 and Cox-2 dissociate in gastric cancer cell lines.
Original language | English (US) |
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Pages (from-to) | 551-556 |
Number of pages | 6 |
Journal | International Journal of Cancer |
Volume | 107 |
Issue number | 4 |
DOIs | |
State | Published - Nov 20 2003 |
Externally published | Yes |
Keywords
- A549
- Carcinogenesis
- Cox-1
- Cox-2
- Cyclooxygenase
- Gastric cancer
- HSC-39
- KATO III
- MKN-1
- MKN-28
- MKN-45
- MKN-7
- MKN-74
- PGES
- Prostaglandin E synthase
ASJC Scopus subject areas
- Cancer Research
- Oncology