Loss of activating transcription factor 3 prevents KRAS-mediated pancreatic cancer.

ABSTRACT: The unfolded protein response (UPR) is activated in pancreatic pathologies and suggested as a target for therapeutic intervention. In this study, we examined activating transcription factor 3 (ATF3), a mediator of the UPR that promotes acinar-to-ductal metaplasia (ADM) in response to pancreatic injury. Since ADM is an initial step in the progression to pancreatic ductal adenocarcinoma (PDAC), we hypothesized that ATF3 is required for initiation and progression of PDAC. We generated mice carrying a germline mutation of Atf3 (Atf3^-/-) combined with acinar-specific induction of oncogenic KRAS (Ptf1a^creERT/+Kras^G12D/+). Atf3^-/- mice with (termed APK) and without KRAS^G12D were exposed to cerulein-induced pancreatitis. In response to recurre

SUBMITTER: Azizi N 

PROVIDER: S-EPMC8173475 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature