ABSTRACT
The ability of pigmentation pathways to induce pigmentation and their alteration in melanoma suggests novel rational approaches for the diagnosis, prevention, and therapy of this disease. When its expression is upregulated in normal melanocytes, microphthalmia-associated transcription factor (MITF) initiates a transcriptional program leading to melanocyte differentiation, enhanced cell cycle arrest, survival, and pigmentation. MITF was itself identified as the product of a gene that affects murine coat color. A majority of melanomas have diminished levels of MITF relative to melanocytes, and high MITF expression may in many contexts inhibit proliferation of melanoma cells. MITF is uniquely poised as a regulator of pigmentation and proliferation/survival. Despite its role in promoting cutaneous photoprotection, roughly 15% to 20% of melanomas have amplifications of MITF. The results suggest that MITF regulates both pigmentation and melanocyte proliferation and survival in a context-dependent manner.
