A series of BRAF- and NRAS-driven murine melanoma cell lines with inducible gene modulation capabilities

ABSTRACT Murine cancer cell lines are powerful research tools to complement studies in genetically engineered mouse models. We have established 21 cell lines from ESC-GEMM chimera melanomas driven by alleles that model the most frequent genetic alterations in human melanoma. Additionally, these cell lines harbor regulatory alleles for the genomic integration of transgenes and the regulation of expression of such transgenes. Here, we report a comprehensive characterization of these cell lines. Specifically, we validated melanocytic origin, driver allele recombination and expression, and activation of the oncogenic MAPK and AKT pathways. We further tested tumor formation in syngeneic immunocompetent recipients as well as functionality of the integrated Tet-ON system and recombination-mediated cassette exchange (RMCE) homing cassette. Finally, by deleting the transcription factor Mafg with an inducible CRISPR/Cas9 approach we demonstrate the utility of the regulatory alleles for candidate gene modulation. These cell lines will be a valuable resource for studying melanoma biology and therapy.