Ras/MAPK signalling intensity defines subclonal fitness in a mouse model of hepatocellular carcinoma.

ABSTRACT: Quantitative differences in signal transduction are to date an understudied feature of tumour heterogeneity. The MAPK Erk pathway, which is activated in a large proportion of human tumours, is a prototypic example of distinct cell fates being driven by signal intensity. We have used primary hepatocyte precursors transformed with different dosages of an oncogenic form of Ras to model subclonal variations in MAPK signalling. Orthotopic allografts of Ras-transformed cells in immunocompromised mice gave rise to fast-growing aggressive tumours, both at the primary location and in the peritoneal cavity. Fluorescent labelling of cells expressing different oncogene levels, and consequently varying levels of MAPK Erk activation, highlighted the selection processes operating at the two sites of tumo

SUBMITTER: Lozano A 

PROVIDER: S-EPMC9891719 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature