Overexpression of midkine in pancreatic duct adenocarcinomas induced by N-nitrosobis(2-oxopropyl) amine in hamsters and their cell lines

The expression of midkine (MK) was investigated in pancreatic ductal hyperp lasias, atypical hyperplasias and adenocarcinomas induced by N-nitrosobis(2 -oxopropyl)amine (BOP) in hamsters, and in hamster ductal adenocarcinoma ce ll lines (HPD-1NR, -2NR and -3NR), MK mRNA was clearly overexpressed in inv asive pancreatic duct adenocarcinomas (PCs) and the three cell lines as ass essed by northern blot analysis, and MK protein expression increased from d uctal hyperplasia through atypical hyperplasias, intraductal carcinomas and invasive PCs by immunohistochemistry. The extent of overexpression of MK m RNA in PCs was almost the same as in hamster whole embryonic tissue. MK is reported to be a retinoid-responsive gene, but MK mRNA expression was not a ffected by treatment with all-trans retinoic acid (tRA) or N-(4-hydroxyphen yl)retinamide (4-HPR) in HPD-1NR cells. The results thus suggest that MK ex pression is involved in the development and progression of pancreatic ducta l adenocarcinomas induced by BOP in hamsters, with loss of upregulation by retinoic acid.