| Summary: | 碩士 === 國立臺灣海洋大學 === 生物科技研究所 === 97 === Pancreatic cancer is the tenth leading cause of cancer death in Taiwan. However, the molecular basis of pancreatic neoplastic transformation has not yet been clearly determined. Activated Kras mutation was the first genetic change detected in the earliest stage of pancreatic intraepithelial neoplasia and in nearly 100% of pancreatic adenocarcinoma. To investigate whether activation of Kras in acinar cells would lead to direct transformation to neoplastic lesions, we generated Elas-CreER; Z/EG; LSL-KrasG12D mice. Furthermore, recent work demonstrated that factors associated with pancreatitis play an important role in acinar transformation and development of intraepithelial neoplastic transformation. Initially, we demonstrated that dexamethasone (DEX) treatment resulted in acinar-to-ductal transdifferentiation in embryonic pancreas and adult mice. Next, we found a large proportion of the neoplastic tissues existed in adult transgenic mice which were GFP-positive suggesting that it was exocrine in origin. Importantly, a subpopulation of neoplastic cells expressed multidrug transporter-ABCG2. We confirmed the findings by analyzing primary pancreatic adenocarcinoma tissue, and found that there were around 5- 8% ABCG2-positive cells existed in adenocarcima tissues indicating it is possibly the cause of drug-resistance and relapse of pancreatic cancer. In summary, the current work demonstrates overexpression of activated Kras mutant in acinar cells would lead to development of pancreatic intraepithelial neoplasia and glucocorticoid-mediated signaling may play an important role.
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