TITLE

Cydooxygenase-2 in Barrett's Esophagus, Barrett's Adenocarcinomas, and Esophageal SCC: Ready for Clinical Trials

AUTHOR(S)
Lord, Reginald V. N.; Danenberg, Kathleen D.; Danenberg, Peter V.; Johnson, David
PUB. DATE
August 1999
SOURCE
American Journal of Gastroenterology;Aug1999, Vol. 94 Issue 8, p2313
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
These studies investigated the role of cyclooxygenase gene expression in esophageal diseases. The study from Germany by Zimmerman et al. detected cytoplasmic cyclooxygenase- 2 (COX-2) protein expression by immunohistochemistry in 156 of 172 (91%) esophageal squamous cell carcinomas (SCC) and in 21 of 27 (78%) Barrett's-associated esophageal adenocarcinomas. There was a wide range in COX-2 immunoreactivity in different cancer specimens, and also within individual specimens. Western blot analysis of COX-2 protein levels was performed for some of the SCC samples, confirming the immunohistochemistry results. No COX-2 protein expression was detected immunohistochemically in Barrett's intestinal metaplasia tissues. There were no significant associations between COX immunoreactivity and tumor stage for either cancer type, except for a higher frequency of local lymph node metastases in SCC patients with low COX-2 expression. In vitro studies using SCC cell lines showed that expression of COX-2 at the mRNA level was associated with production of both COX-2 protein and high prostaglandin (PGE2 and 6-keto-PGFlα) levels. Finally, this study showed that treatment of the COX-2-expressing SCC cells with the COX inhibitors flusolide and NS-398 inhibited prostaglandin synthesis, suppressed proliferative and mitotic activity, and induced widespread apoptosis (the apoptotic effect was assessed with flusolide only). In the non-COX- 2-expressing cell line, none of these effects were observed. The earlier publication, by Wilson et al., from the University of Maryland School of Medicine, used a reverse transcriptase-polymerase chain reaction method to detect elevated COX-2 mRNA levels in 15 of 19 (79%) Barrett's intestinal metaplasia specimens, 2 of 2 (100%) Barrett's dysplasia specimens, and 5 of 5 (100%) Barrett's-associated adenocarcinomas. Increased levels of COX-2 protein, inducible nitric oxide synthase mRNA, and transforming growth factor-α mRNA were also present in similar proportions in Barrett's esophagus and adenocarcinoma tissues.
ACCESSION #
17831210

 

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