Epigenetic silencing of novel tumor suppressors in malignant melanoma
| Autor: | C. Matthew Bradbury, Sekhar Duraisamy, Cara Hobbs, Betsy Nelson, Viswanathan Muthusamy, David P. Curley, Marcus Bosenberg |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Cancer Research Tumor suppressor gene Blotting Western Transplantation Heterologous Melanoma Experimental Mice Nude Biology Decitabine Transfection Epigenesis Genetic Mice Cell Line Tumor medicine Gene silencing Animals Humans Syk Kinase Genetic Predisposition to Disease Epigenetics Gene Silencing RNA Messenger neoplasms Gene Melanoma Cells Cultured Cell Proliferation Homeodomain Proteins Reverse Transcriptase Polymerase Chain Reaction Tumor Suppressor Proteins Intracellular Signaling Peptides and Proteins Cancer Methylation DNA Methylation Protein-Tyrosine Kinases medicine.disease Gene Expression Regulation Neoplastic Oncology DNA methylation Cancer research Azacitidine CpG Islands |
| Zdroj: | Cancer research. 66(23) |
| ISSN: | 0008-5472 |
| Popis: | Malignant melanoma is a common and frequently lethal disease. Current therapeutic interventions have little effect on survival, emphasizing the need for a better understanding of the genetic, epigenetic, and phenotypic changes in melanoma formation and progression. We identified 17 genes that were not previously known to be silenced by methylation in melanoma using a microarray-based screen following treatment of melanoma cell lines with the DNA methylation inhibitor 5-Aza-2′-deoxycytidine. Eight of these genes have not been previously shown to undergo DNA methylation in any form of cancer. Three of the genes, QPCT, CYP1B1, and LXN, are densely methylated in >95% of uncultured melanoma tumor samples. Reexpression of either of two of the silenced genes, HOXB13 and SYK, resulted in reduced colony formation in vitro and diminished tumor formation in vivo, indicating that these genes function as tumor suppressors in melanoma. (Cancer Res 2006; 66(23): 11187-93) |
| Databáze: | OpenAIRE |
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