Oncogenic Braf Induces Melanocyte Senescence and Melanoma in Mice

SummaryWe show here that inducible expression of BrafV600E off the endogenous Braf gene in mouse melanocytes stimulates skin hyperpigmentation and the appearance of nevi harboring senescent melanocytes. Additionally, approximately 70% of BrafV600E mice develop melanomas that reproduce many of the cardinal histological and molecular features of human melanoma and whose cells can colonize the lungs of nude mice. We show that the tumor suppressor p16INK4a is not required to induce melanocyte senescence and that its loss is not required for tumor progression, although it does regulate tumor penetrance and latency. Thus, we have developed a mouse model of melanoma driven by BrafV600E expressed at physiological levels that reflects the genetics and pathology of the human disease