Cyclooxygenase-2 and Bcl-2 expression in the stomach mucosa of Wistar rats exposed to Helicobacter pylori, N'-methyl- N'-nitro- N-nitrosoguanidine and bile.
Cyclooxygenase-2 (COX-2) and Bcl-2 have been implicated in upper gastrointestinal tract carcinomas, but the underlying mechanisms are not known. In the present study we assessed the correlation of COX-2 and Bcl-2 to known cell kinetics in the glandular stomach mucosa of 104 Wistar rats given combinations of Helicobacter pylori, MNNG ( N'-methyl- N'-nitro- N-nitrosoguanidine) and bile. COX-2 expression, Bcl-2 and cell proliferation (Ki-67) in antral and corpus mucosa were determined immunohistochemically. Apoptotic cells were detected using terminal uridine deoxynucleotidyl nick end labelling technique. Expression of COX-2 was found in the lower portion of glandular corpus epithelium, and Bcl-2 positivity was mainly seen in the proliferative zone of both antrum and corpus mucosa. COX-2 expression in histologically normal-appearing corpus mucosa was associated with cell proliferation, atrophy and intestinal metaplasia in antrum and with Bcl-2 expression in corpus mucosa. No correlation was found between apoptosis and Bcl-2 expression. MNNG but not H. pylori significantly increased COX-2 in corpus mucosa. H. pylori, however, promoted the COX-2 expression in corpus when bile was added and Bcl-2 expression in antrum. Abnormal expression of both COX-2 and Bcl-2 seem to be involved in H. pylori-induced gastric carcinogenesis by altering the gastric cell kinetics.
Department of Surgery, Orebro Medical Centre Hospital, 701 85 Orebro, Sweden.
Peter
P
Loogna
Lennart
L
Franzén
Pentti
P
Sipponen
Lennart
L
Domellöf
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001646:Bile / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D051546:Cyclooxygenase 2; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D007527:Isoenzymes; D019253:Proto-Oncogene Proteins c-bcl-2; D008769:Methylnitronitrosoguanidine; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases