Wilson K T, Fu S, Ramanujam K S, Meltzer S J
Department of Medicine, Greenebaum Cancer Center, University of Maryland School of Medicine and Baltimore Veterans Affairs Maryland Health Care System, 21201, USA.
Cancer Res. 1998 Jul 15;58(14):2929-34.
Barrett's esophagus is a premalignant condition arising in response to chronic reflux esophagitis. Inducible nitric oxide synthase (iNOS; NOS-2) and cyclooxygenase-2 (COX-2) are mediators of inflammation and regulators of epithelial cell growth. Expression levels of iNOS and COX-2 are high in colorectal adenomas and carcinomas, and COX-2 expression is elevated in gastric cancers. To determine the involvement of iNOS and COX-2 in Barrett's-associated neoplasia, we measured expression of these genes in metaplastic Barrett's and esophageal adenocarcinomas. We detected elevated iNOS and COX-2 mRNA levels in Barrett's mucosa compared with paired gastric control tissues in 16 of 21 (76%) and 17 of 21 (80%) patients, respectively (P < 0.001 for both genes). In esophageal adenocarcinomas, iNOS and COX-2 mRNA levels were increased in four of five and five of five cases, respectively. Furthermore, in 10 of 10 Barrett's patients, immunohistochemical staining for iNOS and COX-2 expression was strongly positive and higher than in matched gastric controls. Increased COX-2 expression was confirmed by Western blotting. These findings support the hypothesis that iNOS and COX-2 are involved early and often in Barrett's-associated neoplastic progression.
巴雷特食管是一种由慢性反流性食管炎引起的癌前病变。诱导型一氧化氮合酶（iNOS；NOS-2）和环氧化酶-2（COX-2）是炎症介质和上皮细胞生长的调节因子。iNOS和COX-2的表达水平在结直肠腺瘤和癌中较高，且COX-2在胃癌中的表达升高。为了确定iNOS和COX-2在巴雷特相关肿瘤形成中的作用，我们检测了这些基因在化生的巴雷特食管和食管腺癌中的表达。与配对的胃对照组织相比，我们分别在21例患者中的16例（76%）和17例（80%）的巴雷特黏膜中检测到iNOS和COX-2 mRNA水平升高（两个基因的P均<0.001）。在食管腺癌中，iNOS和COX-2 mRNA水平分别在5例中的4例和5例中的5例升高。此外，在10例巴雷特食管患者中，iNOS和COX-2表达的免疫组化染色均呈强阳性，且高于配对的胃对照。通过蛋白质印迹法证实了COX-2表达增加。这些发现支持了iNOS和COX-2早期且常常参与巴雷特相关肿瘤进展的假说。
