[COX-2 associated loss of apoptosis activity in intestinal neoplams in Apc gene knock-out mice].
The aim of the study was to characterize both apoptotic and proliferating cells histologically and to analyze localisation and distribution of various apoptosis-associated proteins in tumours of different stages of degeneration in the animal model of Apc-gene defect mice. Such animals show clinical symptoms similar to those of patients suffering from Familial Adenomatous Polyposis (FAP) but develop the neoplasm's mainly in the small intestine. Tumours from all parts of the gut of 90 days old non-treated MIN-mice were classified as adenocarcinomas, histologically. The apoptosis-associated proteins bax, bcl-2, p53 and the COX-2 enzyme were investigated immunohistochemically. Additionally the localisation and distribution of proliferating (BrdU-labeling) and apoptotic (KLENOW, TUNEL) cells were analysed. In the summary we point out: 1. The activity of apoptosis increases in early stage of neoplasm as a defensive mechanism of mucosa. 2. A decrease in apoptosis rate occurs during carcinogenesis. 3. The inversely correlating, clear COX-2 accumulation accompanying carcinoma development supplies evidence for cyclooxygenase-inhibitor treatment is a promising therapeutic attempt in early stage of FAP.
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D051546:Cyclooxygenase 2; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D017491:Genes, APC / Q000502:physiology*; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D007421:Intestine, Small / Q000473:pathology; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases