Induction of Microphthalmia Transcription Factor (Mitf) by Forskolin and Stimulation of Melanin Release in UISO-Mel-6 Cells

Microphthalmia transcription factor (Mitf) is implicated as the master gene for survival of melanocytes, as well as a key transcription factor regulating the expression of major melanogenic proteins. We have shown that Mitf is a novel prognostic marker in patients with melanoma and that it plays a role in melanoma differentiation. Melanocyte-stimulating hormone up-regulates Mitf expression. Forskolin is a known alpha-melanocyte-stimulating hormone agonist. This study was undertaken to determine if forskolin induces differentiation in UISO-Mel-6 cell lines. Forskolin inhibits cell proliferation and increases the expression of Mitf and tyrosinase related protein-1. It also increases extracellular melanin production. In addition, we showed by flow cytometry that forskolin decrease the number of cells in S-phase without engaging the cells in apoptosis. Our results suggest that Forskolin induces differentiation in melanoma cells via Mitf pathway.