Muc4 loss mitigates epidermal growth factor receptor activity essential for PDAC tumorigenesis.

ABSTRACT: Mucin4 (MUC4) appears early during pancreatic intraepithelial neoplasia-1 (PanIN1), coinciding with the expression of epidermal growth factor receptor-1 (EGFR). The EGFR signaling is required for the onset of Kras-driven pancreatic ductal adenocarcinoma (PDAC); however, the players and mechanisms involved in sustained EGFR signaling in early PanIN lesions remain elusive. We generated a unique Esai-CRISPR-based Muc4 conditional knockout murine model to evaluate its effect on PDAC pathology. The Muc4 depletion in the autochthonous murine model carrying K-ras and p53 mutations (K-ras^G12D; TP53^R172H; Pdx-1cre, KPC) to generate the KPCM4^-/- murine model showed a significant delay in the PanIN lesion formation with a significant reduction (p < 0.01) in EGFR (Y106

SUBMITTER: Bhatia R 

PROVIDER: S-EPMC10198580 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature