Down-regulated melanoma differentiation associated gene (MDA-7) expressionin human melanomas

The melanoma differentiation associated gene-7 (mda-7) has a potential inhi bitory role in melanoma progression, although the mechanisms underlying thi s effect are still unknown. mda-7 mRNA has been found to be present at high er levels in cultured normal melanocytes compared with metastatic melanoma cell lines. Furthermore, levels of mda-7 message have shown an inverse corr elation with melanoma progression in human tumor samples, suggesting that m da-7 may be a novel tumor suppressor gene. We have designed this study to i nvestigate MDA-7 protein expression in different stages of melanoma progres sion and to examine its antiproliferative effects in vitro. Our data demons trate that MDA-7 protein can be found in normal melanocytes and early stage melanomas. It is also observed in smooth muscle cells in the skin. However , in keeping with a possible role as a tumor suppressor, MDA-7 expression i s decreased in more advanced melanomas, with nearly undetectable levels in metastatic disease. We also investigated antitumor effects of overexpressed MDA-7 on human melanoma cells in vitro. Our results demonstrate that Ad-md a-7 induces apoptosis and G2/M cell cycle arrest in melanoma cells, but not in normal human melanocytes. (C) 2001 Wiley-Liss, Inc.