Funkce chromatin-remodelujícího komplexu SWI/SNF v onkogenézi a progresi melanomových buněk

Ondrušová, Ľubica

There is an increasing evidence that alterations in chromatin remodeling play an important role in tumorigenesis. The SWI/SNF chromatin remodeling complexes contribute to the regulation of gene expression by altering the local chromatin structure. Depending on the context, they can act as either transcriptional activators or repressors. All SWI/SNF subcomplexes contain one of two ATPase subunits, Brm (Brahma) or Brg1 (Brahma related gene 1), which provide the energy for remodeling. Malignant melanoma is an aggressive cancer and is known for its notorious resistance to conventional anticancer therapies. MITF (microphthalmia-associated transcription factor) plays an essential role in melanoma biology and is placed on the central crossroad in the regulation of melanocyte development, differentation, maintenance of lineage identity, and survival of both normal and malignant melanocytes. Our results show that the active SWI/SNF complex is strictly required for the expression of MITF. This complex is also required for expression of some transcriptional MITF targets. The survival of melanoma cells is absolutely dependent on functional SWI/SNF complex and all subunits of this complex are expressed at high levels in melanoma cell lines. Primarily, Brg1-containing subcomplexes are more important for MITF...

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