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Expression of microsomal prostaglandin E synthase‐1 in intestinal type gastric adenocarcinoma and in gastric cancer cell lines
Author(s) -
van Rees Bastiaan P.,
Sivula Anna,
Thorén Staffan,
Yokozaki Hiroshi,
Jakobsson PerJohan,
Offerhaus G. Johan A.,
Ristimäki Ari
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.11422
Subject(s) - cancer , carcinogenesis , prostaglandin , cell culture , biology , adenocarcinoma , microsome , prostaglandin e , cancer cell , western blot , medicine , microbiology and biotechnology , endocrinology , cancer research , enzyme , biochemistry , gene , genetics
Gastrointestinal carcinomas synthesize elevated levels of prostaglandin E 2 (PGE 2 ), 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 PGE 2 . 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 PGE 2 . 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. © 2003 Wiley‐Liss, Inc.