Expression analysis of the prostaglandin E2 production pathway in human pancreatic cancers
Expression analysis of the prostaglandin E2 production pathway in human pancreatic cancers
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DOI：
10.1097/mpa.0b013e31816618ba
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发表时间：
2008-08-01
期刊：
影响因子：
2.9
通讯作者：
Eibl, Guido
中科院分区：
文献类型：
--
作者：
Hasan, Sascha;Satake, Makoto;Eibl, Guido
目的：有强有力的证据表明环氧合酶 (COX) 2 和 COX-2 生成的 PGE(2) 在胰腺肿瘤发生过程中发挥重要作用。因此，环加氧酶2已成为胰腺癌的潜在化疗靶点。然而，最近的研究引起了人们对选择性 COX-2 抑制剂安全性的担忧。尽管抑制 COX-2 的益处最终可能超过相关的心血管风险，但有许多替代靶点可抑制人类肿瘤中 PGE(2) 的形成，这些靶点可能对患者危害较小。本研究旨在分析人胰腺癌中参与 PGE2 生成的各种蛋白质的表达。 方法和结果：实时聚合酶链反应和蛋白质印迹分析表明，与匹配的正常胰腺相比，大多数人胰腺癌中细胞质磷脂酶 A2、COX-2、细胞质前列腺素 E 合酶以及微粒体前列腺素 E 合酶 1 和 2 过度表达。免疫组织化学揭示这些蛋白质主要由胰腺癌细胞表达。这些蛋白质的可变表达也在几种人胰腺癌细胞系中得到证实。结论：我们的研究首次证明，参与 PGE2 生成的多种蛋白质在人胰腺癌中过度表达。这些蛋白质可能代表胰腺癌治疗的潜在新靶点。
Objectives: There is strong evidence for an important role of cyclooxygenase (COX) 2 and COX-2-generated PGE(2) during pancreatic tumorigenesis. Cyclooxygenase 2 has therefore become a potential chemotherapeutic target for pancreatic cancer. However, recent studies raised concerns regarding the safety of selective COX-2 inhibitors. Although the benefits of COX-2 inhibition may eventually outweigh the associated cardiovascular risks, there are a number of alternative targets for inhibiting the formation of PGE(2) in human tumors that may prove less harmful to the patient. This study aimed at analyzing the expression of various proteins involved in the generation of PGE2 in human pancreatic cancers.Methods and Results: Real-time polymerase chain reaction and Western blot analyses demonstrated overexpression of cytoplasmic phospholipase A2, COX-2, cytoplasmic prostaglandin E synthase, and microsomal prostaglandin E synthases 1 and 2 in most human pancreatic cancers when compared with matched normal pancreas. Immunohistochemistry revealed expression of these proteins predominantly by pancreatic cancer cells. Variable expression of these proteins was also confirmed in several human pancreatic cancer cell lines.Conclusions: Our studies demonstrated for the first time that various proteins involved in the generation of PGE2 are overexpressed in human pancreatic cancers. These proteins may represent potentially novel targets for the therapy of pancreatic cancers.