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Cancer Biology

Western University

2017

Pancreatitis

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Full-Text Articles in Life Sciences

Contribution Of Activating Transcription Factor 3 To Development Of Acinar-To-Ductal Cell Metaplasia, Jelena Toma Aug 2017

Contribution Of Activating Transcription Factor 3 To Development Of Acinar-To-Ductal Cell Metaplasia, Jelena Toma

Electronic Thesis and Dissertation Repository

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 …


The Loss Of Atrx Creates Susceptibility To Kras-Mediated Pancreatic Damage, Claire C. Young Jun 2017

The Loss Of Atrx Creates Susceptibility To Kras-Mediated Pancreatic Damage, Claire C. Young

Electronic Thesis and Dissertation Repository

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a five-year survival rate of 8%. Oncogenic KRAS mutation is found in greater than 95% of PDAC cases, but additional mutations or injury are required for disease initiation and progression. Chromatin remodeling protein ATRX has been previously implicated in DNA repair, replication and maintaining genomic stability. I hypothesized that loss of ATRX could increase the susceptibility of pancreatic tissue to pancreatic injury or KRAS-mediated damage. In this study, combination of inducible ATRX loss in adult mice with recurrent pancreatic injury or oncogenic KRAS activation resulted in increased pancreatic damage, including fibrosis, …