Methylation status of the SOCS3 gene in human malignant melanomas

Abstract

The suppressors of cytokine signaling (SOCS) family inhibits not only Janus kinase (JAK)/signal transducers and activators of transcription (STAT) but also focal adhesion kinase (FAK) signaling pathways, and has tumor suppressor activity. Aberrant methylation in the promoter region of the SOCS3 gene frequently occurs in several types of human malignancy, and its transcriptional silencing is associated with malignant tumor behavior. In malignant melanomas, the expression and methylation status of the SOCS3 gene have not been elucidated. We therefore examined the methylation status and/or protein expression of the SOCS3 gene in 5 human malignant melanoma cell lines, 2 primary cultures of normal melanocytes, and surgically resected tumors (5 malignant melanomas and 2 melanocytic nevi). Four of the 5 melanoma cell lines and the 2 primary cultures of normal melanocytes expressed SOCS3 protein to various degrees, and only one melanoma cell line was negative. Expression of SOCS3 protein was inversely correlated with methylation status in the SOCS3 promoter region, and treatment with a demethylating agent (5-aza-2'-deoxycytidine) was able to induce expression of the protein in one melanoma cell line that was SOCS3-negative and another that was weakly positive. Three of the 5 primary malignant melanomas and one of the 2 melanocytic nevi showed aberrant methylation. These results suggest that inactivation of the SOCS3 gene by hypermethylation may be involved in the promotion of malignant behavior of melanomas.