Elevated expression of MITF counteracts B-RAF-stimulated melanocyte and melanoma cell proliferation.

Abstract	The protein kinase B-RAF is a human oncogene that is mutated in approximately 70% of human melanomas and transforms mouse melanocytes. Microphthalmia-associated transcription factor (MITF) is an important melanocyte differentiation and survival factor, but its role in melanoma is unclear. In this study, we show that MITF expression is suppressed by oncogenic B-RAF in immortalized mouse and primary human melanocytes. However, low levels of MITF persist in human melanoma cells harboring oncogenic B-RAF, suggesting that additional mechanisms regulate its expression. MITF reexpression in B-RAF-transformed melanocytes inhibits their proliferation. Furthermore, differentiation-inducing factors that elevate MITF expression in melanoma cells inhibit their proliferation, but when MITF up-regulation is prevented by RNA interference, proliferation is not inhibited. These data suggest that MITF is an anti-proliferation factor that is down-regulated by B-RAF signaling and that this is a crucial event for the progression of melanomas that harbor oncogenic B-RAF.
Authors	Claudia Wellbrock, Richard Marais
Journal	The Journal of cell biology (J Cell Biol) Vol. 170 Issue 5 Pg. 703-8 (Aug 29 2005) ISSN: 0021-9525 [Print] United States
PMID	16129781 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	DNA-Binding Proteins MITF protein, human Microphthalmia-Associated Transcription Factor Mitf protein, mouse Transcription Factors Cyclic AMP Proto-Oncogene Proteins B-raf Extracellular Signal-Regulated MAP Kinases
Topics	Animals Cell Line Cell Line, Transformed Cell Proliferation Cyclic AMP (metabolism) DNA-Binding Proteins (genetics, metabolism) Down-Regulation Enzyme Activation Extracellular Signal-Regulated MAP Kinases (metabolism) Humans Melanocytes (cytology, physiology) Melanoma (metabolism, pathology) Mice Microphthalmia-Associated Transcription Factor Proto-Oncogene Proteins B-raf (genetics, metabolism) RNA Interference Signal Transduction (physiology) Transcription Factors (genetics, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!