Electronic Thesis and Dissertation Repository


Master of Science




Dr. Christopher Pin


Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in North America. The highest risk factor for PDAC is recurrent pancreatitis. While the link between PDAC and pancreatitis is unknown, de-differentiation of acinar cells is common to both diseases. Our lab has shown that Activating Transcription Factor 3 (ATF3), a factor upregulated during pancreatic injury, contributes to the development of acinar-to-ductal cell metaplasia (ADM), a precursor phenotype of PDAC. The goal of this study was to identify how ATF3 contributes to ADM. I hypothesize that ATF3 regulates acinar gene expression promoting ADM. We observed decreased ADM development in Atf3-/- acinar cultures, along with expression changes in differentiation genes and ADM promoting pathways (EGFR) in vivo. Assessment following chronic injury indicated absence of ATF3 resulted in decreased tissue damage. These results suggest a novel mechanism where ATF3 promotes ADM through loss of the mature acinar cell phenotype.