SPONTANEOUSLY TRANSFORMED RAT PANCREATIC EPITHELIAL OVAL CELLS GIVE RISE TO DUCTAL TYPE ADENOCARCINOMAS

Oval epithelial cells that proliferate in the pancreas of the rats mai ntained on a copper-deficient diet are considered as stem cells with a potential to differentiate into hepatocytes. We isolated these oval c ells from a copper-deficient rat and maintained these as a cell line i n our laboratory. During 13th passage, oval cells showed increased gro wth and cellular pleomorphism and were analyzed for spontaneous transf ormation by anchorage-independent growth in soft agar and tumorigenici ty in nude mice. Oval cells formed large colonies in soft agar and dev eloped tumors in nude mice after subcutaneous transplantation. The tum ors, by light and electron microscopy, showed features of well differe ntiated ductal-type adenocarcinomas. The phenotypic properties of thes e tumors included expression of neutral mucins, keratin filaments, car cinoembryonic antigen and glutathione S-transferase-pi and absence of gamma-glutamyltranspeptidase. The results of this study demonstrate th at spontaneously transformed oval cells can form typical ductal-type a denocarcinomas. These observations are of particular interest, since b onafide ductal adenocarcinomas have not been described in the rat panc reas before.