Aberrant expression of the maspin gene associated with epigenetic modification in melanoma cells.

Maspin, a mammary serine protease inhibitor, was originally reported to be a tumor suppressor gene in breast and prostate cancers. The expression pattern of the maspin gene differs among cancer types and normal tissue however, and its significance as a tumor suppressor has been questioned. In this study, maspin expression and/or allele-specific methylation status were investigated in five melanoma cell lines and a normal human epidermal melanocyte (NHEM) cell line, and 80 surgically resected tumors (40 melanomas and 40 melanocytic nevi). One (HMV-I) of five melanoma cell lines overexpressed maspin protein whereas the remaining four melanoma cell lines and NHEM did not. The 19 CpG sites of the maspin promoter region were extensively hypomethylated in HMV-I, a maspin-positive cell line, and those of the remaining four melanoma and NHEM cell lines were hypermethylated. Furthermore, maspin-negative cell lines exhibited activation after treatment with 5-aza-2'-deoxycytidine, a DNA demethylating agent. Immunoreactivity for maspin was negative in normal skin melanocytes and 40 melanocytic nevi, but five (12.5%) of 40 melanomas were positive. The methylation status judged by the methylation-specific PCR method was inversely correlated with maspin protein expression in vitro and in vivo. These results suggest that maspin expression in normal skin melanocytes and melanocytic nevi may be repressed in a cell-type-specific manner, whereas maspin is expressed aberrantly in a subset of melanoma cells by epigenetic modification. Further investigations are required to determine the significance of aberrant maspin expression.