Down‐regulated melanoma differentiation associated gene (mda‐7) expression in human melanomas

The melanoma differentiation associated gene‐7 (mda‐7) has a potential inhibitory role in melanoma progression, although the mechanisms underlying this effect are still unknown. mda‐7 mRNA has been found to be present at higher levels in cultured normal melanocytes compared with metastatic melanoma cell lines. Furthermore, levels of mda‐7 message have shown an inverse correlation with melanoma progression in human tumor samples, suggesting that mda‐7 may be a novel tumor suppressor gene. We have designed this study to investigate MDA‐7 protein expression in different stages of melanoma progression and to examine its antiproliferative effects in vitro. Our data demonstrate 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 is 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‐mda‐7 induces apoptosis and G2/M cell cycle arrest in melanoma cells, but not in normal human melanocytes. © 2001 Wiley‐Liss, Inc.