Abstract
SWI/SNF chromatin remodeling complexes contain either Brm (Brahma) or Brg1 (Brahma-related gene 1) as the ATPase subunits. MITF (microphthalmia-associated transcription factor) is a pivotal protein required for the survival and proliferation of normal melanocytes and melanoma cells.
MITF activates transcription of many genes regulating proliferation, apoptosis and invasiveness of melanoma cells and is a potential target for gene therapy of melanoma, an aggressive malignant tumor for which no effective therapy exists when metastases occur. Expression of MITF is absolutely dependent on this the SWI/SNF complex, and both Brg1- or Brm-containing complexes are sufficient to support MITF gene transcription.
Additionally, especially Brg1 complex seems to support tumor growth even independently of the MITF axis. Thus, SWI/SNF complexes appear to be crucial determinants of melanoma development and progression.