Cyclooxygenase-2 mediated regulation of E-cadherin occurs in conventional but not early-onset gastric cancer cell lines.
Cyclooxygenase-2 mediated regulation of E-cadherin occurs in conventional but not early-onset gastric cancer cell lines.
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DOI：
10.3233/clo-2009-0496
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发表时间：
2009
期刊：
影响因子：
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通讯作者：
Milne AN
中科院分区：
文献类型：
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作者：
Sitarz R;Leguit RJ;de Leng WW;Morsink FH;Polkowski WP;Maciejewski R;Offerhaus GJ;Milne AN
背景：COX-2和E-钙粘蛋白参与侵袭和转移，是胃癌发生的关键分子。它们之间的关系在非小细胞肺癌和前列腺癌中有记录。我们提出了胃癌中 COX-2 和 E-钙粘蛋白表达之间关系的新证据。 方法：通过对塞来昔布和 PGE2 处理和未处理的源自肠型肿瘤（MKN45、MKN28、AGS3、MKN7）的胃癌细胞系进行 qPCR 和蛋白质印迹分析，以及组织微阵列 (TMA) 上 178 例胃癌的免疫组织化学，我们检查了 COX-2/E-钙粘蛋白的关系。 结果：塞来昔布下调COX-2导致常规胃癌细胞系中E-钙粘蛋白mRNA和蛋白水平上调，而在早发性胃癌（EOGC）细胞系中表达下调。对 178 例胃癌 TMA 进行的免疫组织化学显示，在常规或早期胃癌组中，COX-2 和 E-cadherin 表达之间没有相关性。 结论：结果表明，COX-2 对胃癌中 E-钙粘蛋白的转录调控有影响，我们的研究结果进一步强调了 EOGC 的有趣性质，它似乎具有与传统胃癌不同的分子表型。此外，我们的研究结果还表明，在胃癌化学预防中使用非甾体抗炎药减少 COX-2 可能仅与老年患者相关。
Background: COX-2 and E-cadherin, involved in invasion and metastasis, are molecules critical for gastric carcinogenesis. A relationship between them is documented in non-small cell lung and prostate cancer. We present novel evidence of a relationship between COX-2 and E-cadherin expression in gastric cancer. Methods: Using qPCR and Western blots analysis on celecoxib and PGE2 treated and untreated gastric cancer cell lines derived from tumours of the intestinal type (MKN45, MKN28, AGS3, MKN7) and immunohistochemistry of 178 gastric cancers on tissue microarrays (TMA), we examined the COX-2/E-cadherin relationship. Results: Down-regulation of COX-2 by celecoxib led to up-regulation of E-cadherin mRNA and protein levels in conventional gastric cancer cell lines, whereas expression was down regulated in the early-onset gastric cancer (EOGC) cell line. Immunohistochemistry on TMAs of 178 gastric cancers showed no correlation between COX-2 and E-cadherin expression in the conventional or early gastric cancer groups. Conclusions: The results suggest that COX-2 has an impact on transcriptional regulation of E-cadherin in gastric cancer and our findings further highlight the intriguing nature of EOGCs which appear to have a molecular phenotype distinct from conventional gastric cancer. In addition, our findings also suggest that reduction of COX-2 using nonsteroidal anti-inflammatory drugs in gastric cancer chemoprevention may only be relevant for older patients.