Ristimäki A, Honkanen N, Jänkälä H, Sipponen P, Härkönen M
Department of Clinical Chemistry, University of Helsinki, Finland.
Cancer Res. 1997 Apr 1;57(7):1276-80.
Epidemiological studies suggest that the use of aspirin decreases the incidence of and mortality from gastrointestinal cancers. The best known target of aspirin and other nonsteroidal anti-inflammatory drugs is cyclooxygenase (Cox), the rate-limiting enzyme in the conversion of arachidonic acid to prostanoids. Two Cox genes have been cloned, of which Cox-2 is an inducible immediate-early gene. It is still unknown how nonsteroidal anti-inflammatory drugs act as chemopreventive agents, but they may target Cox-2. Cox-2 mRNA and protein were recently found to be expressed in human colon carcinoma. We have now studied the expression of Cox-2 in human gastric adenocarcinoma tissues which contained significantly higher levels of Cox-2 mRNA when compared with paired gastric mucosal specimens devoid of cancer cells. In contrast, Cox-1 mRNA levels were not elevated in the carcinoma. However, Cox-2 mRNA was not expressed in mucinous ovarian carcinoma samples as detected by Northern blot hybridization. Immunohistological detection of Cox-2 protein showed cytoplasmic staining in the gastric carcinoma cells but not in the surrounding stroma. Some hyperplastic glands showed intense staining, whereas glands of normal morphology were negative. Our data thus suggest that Cox-2 is expressed by human gastric adenocarcinoma.
流行病学研究表明，使用阿司匹林可降低胃肠道癌症的发病率和死亡率。阿司匹林及其他非甾体抗炎药最广为人知的靶点是环氧合酶（Cox），它是花生四烯酸转化为前列腺素过程中的限速酶。已克隆出两种Cox基因，其中Cox-2是一种可诱导的即早基因。非甾体抗炎药作为化学预防剂的作用机制尚不清楚，但它们可能靶向Cox-2。最近发现Cox-2 mRNA和蛋白在人结肠癌中表达。我们现在研究了Cox-2在人胃腺癌组织中的表达，与配对的无癌细胞的胃黏膜标本相比，胃腺癌组织中Cox-2 mRNA水平显著更高。相比之下，癌组织中Cox-1 mRNA水平并未升高。然而，通过Northern印迹杂交检测发现，黏液性卵巢癌样本中未表达Cox-2 mRNA。Cox-2蛋白的免疫组织化学检测显示，胃癌细胞中有细胞质染色，而周围基质中没有。一些增生性腺管显示强烈染色，而形态正常的腺管为阴性。因此，我们的数据表明人胃腺癌表达Cox-2。
