%0 Journal Article
%A Hahm, Ki-Baik
%A Lim, Ho-Yeong
%A Sohn, Seonghyang
%A Kwon, Hyuk-Jae
%A Lee, Ki-Myung
%A Lee, Jeong-Sang
%A Surh, Young-Joon
%A Kim, Young-Bae
%A Joo, Hee-Jae
%A Kim, Won-Seok
%A Cho, Seung-Won
%D 2002
%I Begell House
%N 2
%P 12
%R 10.1615/JEnvironPatholToxicolOncol.v21.i2.100
%T In Vitro Evidence of the Role of COX-2 in Attenuating Gastric Inflammation and Promoting Gastric Carcinogenesis
%U https://www.dl.begellhouse.com/journals/0ff459a57a4c08d0,4ac6c8531cba5202,1eca7d1e52e1dd2e.html
%V 21
%X Although gastric adenocarcinoma is one of the most common malignancies in the world, little is known about its exact molecular processes in development and progression. Recent studies suggest that COX-2 is important in carcinogenesis of gastrointestinal cancers, and is especially involved in carcinogenesis in a mouse model of familial adenomatosis polyposis. To understand the role of COX-2 in gastric carcinogenesis and Helicobacter pylori-associated gastritis, we measured COX-2 expression in 170 human gastric carcinoma tissues by immunohistochemical analysis and compared the expression of COX-2 in paired tissues obtained from normal-looking and cancer-bearing mucosa. Further evidence of the involvement of COX-2 in gastritis and gastric carcinogenesis was obtained by establishing stable cell lines overexpressing COX-2. After subcloning of COX-2 into pCB7 mammalian expression vector, two stable cell lines named MKN-28-COX-2 and MKN-45-COX-2 were generated by transfection of COX-2 cDNA. To understand the effect of COX-2 on gastritis, we performed an electrophoretic mobility shift assay of NF-kB (inflammation-associated transcription factor), and measured malondialdehyde levels and chemiluminescence activities in both mock-transfected MKN and MKN-COX-2 cells after stimulation of H. pylori (1 x 106 CFU/mL) and neutrophils (102 cells/mL). A marked attenuation ofNF-kB bindings and generation of free radicals was observed in COX-2 overexpressed cells. Another set of experiments, including the growth inhibition by TGF-b treatment, Matrigel invasion assay, and apoptosis assay, was done. COX-2 showed the advantage of the escape from the growth inhibition by TGF-b through decreasing TGF-b RII expression and increased cell invasiveness. In conclusion, COX-2 expression seems to be induced to attenuate the degree of atrophic gastritis, the initial event in gastric carcinogenesis, and promote gastric carcinogenesis.
%8 2002-06-01