Journal of Environmental Pathology, Toxicology and Oncology

ISSN for PRINT: 0731-8898

For Online Access

Best Paper Award Selection - Editorial Board Site

2002, Volume21

Issue 2

124 pages

Issue price - $160.00

Ki-Baik Hahm
Departments of Gastroenterology, Ajou University School of Medicine, Suwon, Korea

Ho-Yeong Lim
Departments of Oncology, Ajou University School of Medicine, Suwon, Korea

Seonghyang Sohn
Departments of Dermatology, Ajou University School of Medicine, Suwon, Korea

Hyuk-Jae Kwon
Departments of Dermatology, Ajou University School of Medicine, Suwon, Korea

Ki-Myung Lee
Departments of Gastroenterology, Ajou University School of Medicine, Suwon, Korea

Jeong-Sang Lee
College of Pharmacology, Seoul National University, Seoul, Korea

Young-Joon Surh, Ph.D., Professor
National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy Seoul National University Shinlim-dong, Kwanak-gu Seoul 151-742 South Korea

Young-Bae Kim
Departments of Pathology,5 Ajou University School of Medicine, Suwon, Korea

Hee-Jae Joo
Departments of Pathology,5 Ajou University School of Medicine, Suwon, Korea

Won-Seok Kim
Departments of Gastroenterology, Ajou University School of Medicine, Suwon, Korea

Seung-Won Cho
Departments of Gastroenterology, Ajou University School of Medicine, Suwon, Korea

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.

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