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.
Lekmine
Fatima
F
Department of Surgical Oncology, University of Illinois at Chicago, Chicago, Illinois 60612, USA. fatimal@uic.edu
Salti
George I
GI
D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology*; D006801:Humans; D008543:Melanins / Q000096:biosynthesis*; D009074:Melanocyte-Stimulating Hormones / Q000819:agonists*; D008545:Melanoma; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics*
D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D005576:Colforsin; D009074:Melanocyte-Stimulating Hormones