Methyl-binding domain protein 2 (MBD2) is important for repression of hypermethylated genes and cell survival in malignant melanoma
Methylation of cytosines in promoter CpG islands is an important mechanism for inactivation of tumor suppressor genes in human cancer. The methylation patterns are read and interpreted by methyl-binding domain proteins (MBDs), a group of proteins that repress transcription in a methylation-dependent and sequence-specific manner. Among these proteins, MBD2 is a particularly attractive anticancer target since MBD2 knockout mice are viable and resistant to tumorigenesis. Here, we have studied the role of MBD2 in cellular growth and repression of hypermethylated genes in malignant melanoma. Specifically, we have developed systems for transient, stable and inducible knockdown of MBD2 in melanoma cell lines. Our data shows that MDB2 is important for methylation-dependent silencing of certain tumor suppressor genes in melanoma cell lines, and that knockdown of MBD2 induces extensive cell death. Our data identifies MBD2 as a potential therapeutic target in melanoma.
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Document Type: Abstract
Publication date: May 1, 2008