Okuyama T, Ishihara S, Sato H, Rumi M A K, Kawashima K, Miyaoka Y, Suetsugu H, Kazumori H, Cava C F Ortega, Kadowaki Y, Fukuda R, Kinoshita Y
Second Department of Internal Medicine, Shimane Medical University, Izumo, Shimane, Japan.
J Lab Clin Med. 2002 Aug;140(2):92-102. doi: 10.1067/mlc.2002.125784.
The effect of prostaglandin E2 (PGE2) on the proliferation of gastric cancer cells is still unclear. PGE2 receptors are divided into four subtypes - EP1, EP2, EP3, and EP4 - which are coupled to three different intracellular signal-transduction systems. Stimulation of EP2 and EP4 is linked with cyclic adenosine 3', 5'-monophosphate (cAMP)-dependent protein kinase A (PKA). In some human gastric cancer cells, PGE2 has been suggested to have an antiproliferative effect by way of increased cAMP production. Expression of EP2 and EP4 in human gastric carcinoma cells, however, has not been examined. We examined the expression of EP2 and EP4 and the antiproliferative effects of specific EP2 and EP4 agonists on four different human gastric cancer cell lines. Our data clarified that all the cell lines investigated in this study expressed EP2 and EP4 and that the specific agonists of these receptors induced growth inhibition with an accompanying increase in cAMP production. In summary, gastric cancer cells have EP2 and EP4 receptors, and their selective activation is linked with the decreased cell proliferation.
前列腺素E2（PGE2）对胃癌细胞增殖的影响仍不清楚。PGE2受体分为四种亚型——EP1、EP2、EP3和EP4——它们与三种不同的细胞内信号转导系统偶联。EP2和EP4的刺激与环磷酸腺苷（cAMP）依赖性蛋白激酶A（PKA）相关。在一些人胃癌细胞中，有人提出PGE2通过增加cAMP生成而具有抗增殖作用。然而，EP2和EP4在人胃癌细胞中的表达尚未得到检测。我们检测了EP2和EP4的表达以及特定EP2和EP4激动剂对四种不同人胃癌细胞系的抗增殖作用。我们的数据表明，本研究中所研究的所有细胞系均表达EP2和EP4，并且这些受体的特异性激动剂可诱导生长抑制并伴随cAMP生成增加。总之，胃癌细胞具有EP2和EP4受体，其选择性激活与细胞增殖减少有关。
