Quantitative, tissue-specific analysis of cyclooxygenase gene expression in the pathogenesis of Barrett's adenocarcinoma.
Cyclooxygenase (Cox-2) is implicated in the pathogenesis of many cancers including esophageal adenocarcinoma (EAC), whereas the role of the isoform Cox-1 in carcinogenesis is not well understood. To further elucidate the role of these factors in the development of EAC, we measured the gene expressions (mRNA levels) of Cox-2 and Cox-1 by real-time quantitative polymerase chain reaction (QRT-PCR) in tissues from normal esophagus with and without erosive gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), dysplasia, adenocarcinoma, and in healthy gastric antrum. All tissues were purified by laser capture microdissection from endoscopic or surgical resection specimens. Median Cox-2 gene expression did not differ significantly among the esophageal control groups but was elevated 5-fold in BE, 8-fold in dysplasia and 16-fold in EAC compared to normal esophageal controls with no erosive GERD. Erosive GERD tissue had slightly higher median Cox-2 expression but Cox-2 expression in normal antrum was much higher than that in a normal esophagus, close to that of dysplasia. In contrast to that of Cox-2, Cox-1 expression was significantly decreased in all neoplastic tissues compared to normal controls. Cox-1 and Cox-2 expression varied over a wide range in the neoplastic tissues but over a relatively narrow range in the esophageal normal tissues. The occurrence of substantial alterations in Cox-1 and Cox-2 expression at the BE stage indicates that these are early events in the development of EAC. These results confirm the important role of Cox-2 amplification in the pathogenesis of esophageal adenocarcinoma, but the unexpected down-regulation of Cox-1 raises questions about its role in carcinogenesis.
Kuramochi
Hidekazu
H
From the Department of Biochemistry and Molecular Biology, USC/Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Vallböhmer
Daniel
D
Uchida
Kazumi
K
Schneider
Sylke
S
Hamoui
Nahid
N
Shimizu
Daisuke
D
Chandrasoma
Parakrama T
PT
DeMeester
Tom R
TR
Danenberg
Kathleen D
KD
Danenberg
Peter V
PV
Peters
Jeffrey H
JH
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D001471:Barrett Esophagus / Q000235:genetics* / Q000473:pathology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D004942:Esophagitis, Peptic / Q000235:genetics / Q000473:pathology; D004947:Esophagus / Q000473:pathology; D005764:Gastroesophageal Reflux / Q000235:genetics / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins; D010544:Peroxidases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis
D008565:Membrane Proteins; D012333:RNA, Messenger; D010544:Peroxidases; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases