Fbxw7 Deletion Accelerates Kras^G12D-Driven Pancreatic Tumorigenesis via Yap Accumulation.

ABSTRACT: Pancreatic cancers driven by KRAS mutations require additional mutations for tumor progression. The tumor suppressor FBXW7 is altered in pancreatic cancers, but its contribution to pancreatic tumorigenesis is unknown. To determine potential cooperation between Kras mutation and Fbxw7 inactivation in pancreatic tumorigenesis, we generated P48-Cre;LSL-Kras^G12D;Fbxw7^fl/fl (KFC^fl/fl) compound mice. We found that KFC^fl/fl mice displayed accelerated tumorigenesis: all mice succumbed to pancreatic ductal adenocarcinoma (PDA) by 40 days of age, with PDA onset occurring by 2 weeks of age. PDA in KFC^fl/fl mice was preceded by earlier onset of acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN) lesions, and associat

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC5071541 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature