Activation of WNT/β-Catenin Signaling Enhances Pancreatic Cancer Development and the Malignant Potential Via Up-regulation of Cyr61.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC), a poor prognostic cancer, commonly develops following activating mutations in the KRAS oncogene. Activation of WNT signaling is also commonly observed in PDAC. To ascertain the impact of postnatal activation of WNT-stimulated signaling pathways in PDAC development, we combined the Elastase-tva-based RCAS-TVA pancreatic cancer model with the established LSL-Kras^G12D, Ptf1a-cre model. Delivery of RCAS viruses encoding β-catenin^S37A and WNT1 stimulated the progression of premalignant pancreatic intraepithelial neoplasias (PanIN) and PDAC development. Moreover, mice injected with RCAS-β-catenin^S37A or RCAS-Wnt1 had reduced survival relative to RCAS-GFP-injected controls (P<.05). Ectopic expression of active β-catenin, or

SUBMITTER: Sano M 

PROVIDER: S-EPMC5126137 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature