Role of Acinar Cell in Hamster Pancreatic Carcinogenesis

Park, Byung Kyu; Chung, Hye Won; Song, Si Young; Park, Seung Woo; Chung, Jae Bock; Kang, Jin Kyung; Lee, Ji Eun; Kim, Sun A; Kim, Han Soo

Abstract

BACKGROUND/AIMS: Considerable doubts still remain about the earliest lesions and particularly, the cell origin of pancreatic cancer. In this study, we investigated the serial morphologic and cellular changes, and the expression of cyclin D1 in a hamster model with pancreatic carcinogenesis induced by N-nitrosobis (2-oxopropyl) amine (BOP). METHODS: Twelve Syrian Golden hamsters were administered 15 mg/kg of BOP weekly for 12 weeks. They were serially sacrificed at 16, 20, and 24 weeks. The specimens of the pancreas were examined for pathologic changes and stained with cyclin D1 and BrdU monoclonal antibody. RESULTS: The serial morphologic changes were gradual loss of acinar cells, progressively increased tubular complexes, and perilobular and intralobular fibrosis with the lapse of time. These newly developed transformed tubular ductal structures seemed to be originated from the acinar cells. The cyclin D1 overexpression and intense BrdU labeling were observed in the early event of tubular complex formation. CONCLUSIONS: Pancreatic ductal adenocarcinoma may be originated from the acinar cells via possible transdifferentiation from acinar cell to ductal cell or proliferation of multipotent stem cells located in the acini. The overexpression of cyclin D1 may play a major role in the early stage of carcinogenic process in BOP-induced hamster pancreatic cancer.