Expression of microsomal prostaglandin E synthase-1 in intestinal type gastric adenocarcinoma and in gastric cancer cell lines.
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-1beta (IL-1beta) 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.
van Rees
Bastiaan P
BP
Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
Sivula
Anna
A
Thorén
Staffan
S
Yokozaki
Hiroshi
H
Jakobsson
Per-Johan
PJ
Offerhaus
G Johan A
GJ
Ristimäki
Ari
A
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D015152:Blotting, Northern; D015153:Blotting, Western; D002273:Carcinogens / Q000494:pharmacology; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004790:Enzyme Induction; D005753:Gastric Mucosa / Q000201:enzymology / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D007422:Intestines / Q000201:enzymology / Q000473:pathology; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D008565:Membrane Proteins; D008861:Microsomes / Q000201:enzymology*; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate