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Metallothionein 1E is methylated in malignant melanoma and increases sensitivity to cisplatin-induced apoptosis

Metallothionein 1E is methylated in malignant melanoma and increases sensitivity to cisplatin-induced apoptosis

Authors :
Gabriela Gremel
William M. Gallagher
Shauna Hegarty
Mario F. Fraga
Manel Esteller
Peter A. Dervan
William J. Faller
Denise Ryan
Mairin Rafferty
Source :
Melanoma Research. 20:392-400
Publication Year :
2010
Publisher :
Ovid Technologies (Wolters Kluwer Health), 2010.

Abstract

DNA methylation plays a major role in cancer by silencing tumour suppressor genes. In melanoma, only a discrete number of methylated genes have been identified so far. After the treatment of melanoma cells with a DNA methyltransferase inhibitor and subsequent transcriptomic profiling, we had identified earlier a cohort of melanoma progression-associated genes regulated by methylation. Here, we identified which of these genes are directly methylated in melanoma cell lines and tissues. First, we examined 16 genes by bisulphite sequencing in the WM793 isogenic cell line model series. Five of these genes (CYBA, FABP5, MT1E, TSPY1 and TAC1) displayed increased methylation in several invasive cell lines compared with the parental WM793 cells, indicating their involvement in progression. Next, we analyzed several matched primary/metastatic tumours using methylation-specific PCR, which revealed that MT1E (one of the five genes assessed) was methylated in the largest proportion of tumours. Examination of a larger cohort of samples showed that 1 of 17 (6%) of the benign naevi, 16 of 43 (37%) primary tumours and 6 of 13 (46%) of the metastases displayed MT1E methylation. In addition, ectopic over-expression of MT1E mediated sensitization to cisplatin-induced apoptosis. Overall, these studies suggest that MT1E is a potential tumour suppressor gene, whose loss may promote resistance to apoptosis-inducing therapies.

Details

ISSN :
09608931
Volume :
20
Database :
OpenAIRE
Journal :
Melanoma Research
Accession number :
edsair.doi...........d1dd5252cba6986d3ff0b2b9048bba03
Full Text :
https://doi.org/10.1097/cmr.0b013e32833d32a6