%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