Expression of microsomal prostaglandin E synthase-1 in intestinal type gastric adenocarcinoma and in gastric cancer cell lines

Bastiaan P. Van Rees, Anna Sivula, Staffan Thorén, Hiroshi Yokozaki, Per Johan Jakobsson, G. Johan A Offerhaus, Ari Ristimäki

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)551-556
Number of pages6
JournalInternational Journal of Cancer
Volume107
Issue number4
DOIs
StatePublished - Nov 20 2003
Externally publishedYes

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

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