van Rees Bastiaan P, Sivula Anna, Thorén Staffan, Yokozaki Hiroshi, Jakobsson Per-Johan, Offerhaus G Johan A, Ristimäki Ari
Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
Int J Cancer. 2003 Nov 20;107(4):551-6. doi: 10.1002/ijc.11422.
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.
胃肠道癌合成的前列腺素E2（PGE2）水平升高，其在机制上与致癌作用相关。最近，微粒体前列腺素E合酶-1（mPGES-1）被克隆，它似乎是可诱导的，并且在PGE2的生物合成中与环氧化酶-2（Cox-2）相关。我们检测了mPGES-1在肠型胃腺癌及胃癌细胞系中的表达。通过Northern印迹分析检测，57%（4/7）的胃癌中mPGES-1转录本升高。通过免疫组织化学检测，56%（5/9）的癌中观察到中度至强的mPGES-1免疫反应性。此外，在源自肠型肿瘤的胃腺癌细胞系（MKN-7和MKN-28）中检测到mPGES-1 mRNA、蛋白及微粒体PGES活性。然而，与Cox-2不同，在所检测的任何胃癌细胞系（MKN-1、-7、-28、-45和-74）中，佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）或白细胞介素-1β（IL-1β）均未诱导mPGES-1 mRNA或蛋白的表达。两个胃癌细胞系（MKN-45和MKN-74）不表达mPGES-1且缺乏微粒体PGES活性，但仍能够合成PGE2。因为通过免疫印迹检测所有胃细胞系均表达胞质型PGES（cPGES），所以Cox-2有可能在胃癌细胞中与cPGES或其他尚未鉴定的PGES相互作用。此外，我们的数据表明，驱动mPGES-1和Cox-2表达的调控机制在胃癌细胞系中是分离的。
