Increased expression of inducible nitric oxide synthase and cyclooxygenase-2 in Barrett's esophagus and associated adenocarcinomas.
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.
Department of Medicine, Greenebaum Cancer Center, University of Maryland School of Medicine and Baltimore Veterans Affairs Maryland Health Care System, 21201, USA. kwilson@umaryland.edu
K T
KT
Wilson
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S
Fu
K S
KS
Ramanujam
S J
SJ
Meltzer
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D001471:Barrett Esophagus / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D051546:Cyclooxygenase 2; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis* / Q000378:metabolism; D008565:Membrane Proteins; D009363:Neoplasm Proteins / Q000032:analysis* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000032:analysis* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*
D007527:Isoenzymes; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases