Mechanistic analysis of pancreatic ductal carcinogenesis in hamsters.
In this article, we introduce our rapid-production model for pancreatic duct adenocarcinomas and describe the mechanisms of pancreatic duct carcinogenesis so far elucidated in Syrian golden hamsters. It is evident that a series of histogenetic steps are involved, leading from hyperplasia through atypical hyperplasia to intraductal carcinoma and invasive carcinoma. As DNA alters, K-ras mutation appears to be an early event, whereas p53 mutations generally occur in the tumor-progression phase. The induced cancer cells may show autocrine growth, secreting TGF-alpha and vascular endothelial growth factor (VEGF), and are immortalized with a shortened TRF length and increased telomerase activity. The rapid-production model of pancreatic duct adenocarcinomas has not only provided a major stimulus to understanding induction mechanisms but should also serve as a bioassay to facilitate the identification of dietary risk factors and the search for appropriate chemopreventive or chemotherapeutic agents or both to help control this deadly disease.
Konishi
Y
Y
Department of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara, Japan.
Tsutsumi
M
M
Tsujiuchi
T
T
D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D000818:Animals; D002273:Carcinogens; D006224:Cricetinae; D004195:Disease Models, Animal; D006965:Hyperplasia; D008647:Mesocricetus; D009154:Mutation; D009602:Nitrosamines / Q000008:administration & dosage; D010183:Pancreatic Ducts / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D011312:Pressure
D002273:Carcinogens; D009602:Nitrosamines; C013622:nitrosobis(2-oxopropyl)amine