Absence of Enhancer of Zeste Homolog 2 Promotes the Progression of KRAS-Driven Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is estimated to be the second deadliest cancer by 2030. Previous studies showed constitutive activation of KRAS (KRASG12D) is a key genetic driver of PDAC, accelerated by deletion of the epigenetic regulator Enhancer of Zeste Homologue 2 (EZH2). However, contradictory findings suggest multiple roles for EZH2. The goal of this study was to define EZH2’s contributes to early KRASG12D-driven PDAC. I hypothesized that EZH2 restricts KRASG12D initiation of PDAC in response to injury. To address this hypothesis, genetically modified mice with targeted deletion of the SET domain of Ezh2 +/- KRASG12D were exposed to cerulein-induced pancreatic injury and examined for pancreatic lesions. Histological analysis for markers of tissue damage and inflammation showed loss of EZH2 caused no difference in the pre-neoplastic lesion formation but did affect progression, and reduced immune cell infiltration, suggesting a role for EZH2 in limiting early progression of KRASG12D-mediated PDAC.

Name thesis:degree_name

M Sc

Discipline thesis:degree_discipline

Physiology and Pharmacology

Grantor dc:publisher

The University of Western Ontario

Year dc:date.issued

2022

Author dc:creator

• Wang, Xiaoyi

Advisor dc:contributor.advisor

• Christopher Pin

• PDAC
• EZH2
• KRAS
• pancreatitis.

Language dc:language.iso

en_ca

Handle dc:identifier.uri

https://hdl.handle.net/20.500.14721/32490

OAI identifier oai:identifier

oai:uwo.scholaris.ca:20.500.14721/32490