Pancreatic Cells Are Resistant to KRASQ61L Expression due to Hyperactive ERK/MAPK Signaling and Apoptosis Induction.

ABSTRACT: The RAS family of small GTPases is among the most frequently mutated gene families in human cancer. In pancreatic ductal adenocarcinoma (PDAC), ∼95% of cases harbor an activating KRAS mutation, primarily at codon 12, 13, or 61, with G12D being the most common overall (40%). In contrast, the KRASQ61L mutation, though constitutively active, is virtually absent in tumors of patients with PDAC. This suggests that KRASQ61L may engage in distinct, allele-specific signaling that limits its ability to drive tumorigenesis. Determining the mechanisms that limit the occurrence of this mutation will aid in our understanding of the critical KRAS effectors and pathways that drive tumorigenesis. To investigate these mechanisms, we utilized a tightly controlled doxycycline-inducible KRAS expression system

SUBMITTER: Burge RA 

PROVIDER: S-EPMC12541299 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature