Aberrant expression of MSG1 transcriptional activator in human malignant melanoma in vivo

MSG1 was originally isolated as a candidate pigmentation-related gene. MSG1 mRNA transcripts were expressed strongly in cultured human and mouse norma l epidermal melanocytes, and in highly pigmented mouse melanoma cells, whil e its expression was very weak in cultured non-pigmented human melanoma cel ls. Thus, MSG1 was initially proposed to be a melanocyte-specific gene, and its possible role in pigmentation has been speculated. It was found recent ly that the MSG1 protein interacts functionally with Smad4, which plays a p ivotal role in signal transduction of transforming growth factor-p, In this study, we analyzed MSG1 protein expression by immunohistochemistry using h uman tumor samples from nevus and malignant melanoma to reveal its role in pigmentation and melanoma development in vivo. A relatively strong but hete rogeneous expression of MSG1 protein was seen in melanomas compared with we ak expression in nevi, In nevi, MSG1 expression was mostly confined to the pigmented region, while it was expressed in both pigmented and non-pigmente d regions in melanoma, Intracellularly, MSG1 protein was localized in the c ytoplasm of nevus cells, but was seen in both nuclei and cytoplasm of melan oma cells. These results support a hypothesis that MSG1 plays a role in pig mentation. It is also suggested that MSG1 may be involved in malignant tran sformation of pigment cells. Alternatively, the aberrant expression of MSG1 in melanoma cells might be due to the abnormal environment, including aber rant cytokine or growth factor expression, associated with melanoma formati on.