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.
Ekmekcioglu
S
S
Department of Molecular and Cellular Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Ellerhorst
J
J
Mhashilkar
A M
AM
Sahin
A A
AA
Read
C M
CM
Prieto
V G
VG
Chada
S
S
Grimm
E A
EA
D017209:Apoptosis; D002454:Cell Differentiation; D002455:Cell Division; D003593:Cytoplasm / Q000737:chemistry; D015536:Down-Regulation; D016195:G2 Phase; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006133:Growth Substances / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007378:Interleukins; D008544:Melanocytes / Q000737:chemistry*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D008938:Mitosis; D014407:Tumor Cells, Cultured; D000099180:Interleukin-24
D006133:Growth Substances; D007378:Interleukins; D000099180:Interleukin-24