Melanocytic nevus-like hyperplasia and melanoma in transgenic BRAFV600E mice

摘要: BRAF, a cellular oncogene and effector of RAS-mediated signaling, is activated by mutation in ∼60% melanomas. Most these mutations consist V600E substitution resulting constitutive kinase activation. Mutant BRAF thus represents an important therapeutic target melanoma. In effort to produce pre-clinical model mutant function melanoma, we have generated mouse expressing targeted melanocytes. We show that transgenic mice, widespread benign melanocytic hyperplasia with histological features nevi occurs, biochemical evidence senescence. Melanocytic progresses overt melanoma incidence dependent on expression levels. Melanomas CDKN2A loss, genetic disruption the locus greatly enhances formation, consistent collaboration between activation loss suggested from studies human The development also involves Mapk Akt signaling pathways senescence, findings faithfully recapitulate those seen This murine BRAF-induced formation provides tool for identifying further alterations cooperates may be useful enhancing susceptibility BRAF-targeted therapeutics