Increasing cyclooxygenase-2 (cox-2) gene expression in the progression of Barrett's esophagus to adenocarcinoma correlates with that of Bcl-2.
Previous studies from our laboratory and others have suggested that increased expression of cox-2 is important in the genesis of esophageal adenocarcinoma. In vitro studies suggest that cox-2 regulates expression of the anti-apoptotic protein bcl-2, thus possibly accounting for reduced apoptosis in carcinogenesis. The aim of this study was to investigate the relationship of these 2 genes in the development of Barrett's-associated adenocarcinoma. Histologic sections from endoscopic biopsies or esophagectomy specimens were classified as non-dysplastic Barrett's (n = 30), intraepithelial neoplasia (n = 12) and adenocarcinoma (n = 48). The desired tissue was isolated by laser capture microdissection and expression levels of cox-2 and bcl-2 were measured by quantitative real-time PCR (Taqman). Gene expression levels were compared to samples of the distal esophageal squamous epithelium (n = 55) and reflux-esophagitis (n = 25), without Barrett's or cancer. Expression of both bcl-2 and cox-2 were increased in non-dysplastic Barrett's (p = 0.0077, p = 0.0037), intraepithelial neoplasia (p = 0.0053, p = 0.0220) and adenocarcinoma (p < 0.0001, p < 0.0001) compared to squamous epithelium or reflux-esophagitis. Furthermore, there is a significant correlation between these two genes, especially in carcinoma (p < 0.0001).
Department of Biochemistry and Molecular Biology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA.
Daisuke
D
Shimizu
Daniel
D
Vallböhmer
Hidekazu
H
Kuramochi
Kazumi
K
Uchida
Sylke
S
Schneider
Parakrama T
PT
Chandrasoma
Hiroshi
H
Shimada
Tom R
TR
DeMeester
Kathleen D
KD
Danenberg
Jeffrey H
JH
Peters
Steven R
SR
DeMeester
Peter V
PV
Danenberg
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D001471:Barrett Esophagus / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*
D019253:Proto-Oncogene Proteins c-bcl-2; D051546:Cyclooxygenase 2