Down-regulated melanoma differentiation associated gene (MDA-7) expression in human melanomas
Down-regulated melanoma differentiation associated gene (MDA-7) expression in human melanomas
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DOI：
10.1002/ijc.1437
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发表时间：
2001-10-01
影响因子：
6.4
通讯作者：
Grimm, EA
中科院分区：
文献类型：
--
作者：
Ekmekcioglu, S;Ellerhorst, J;Grimm, EA
黑色素瘤分化相关基因 7 (mda-7) 在黑色素瘤进展中具有潜在的抑制作用，尽管这种作用的机制尚不清楚。研究发现，与转移性黑色素瘤细胞系相比，培养的正常黑色素细胞中 mda-7 mRNA 的含量更高。此外，mda-7 信息水平与人类肿瘤样本中的黑色素瘤进展呈负相关，表明 mda-7 可能是一种新型肿瘤抑制基因。我们设计这项研究的目的是调查黑色素瘤进展不同阶段的 MDA-7 蛋白表达，并检查其体外抗增殖作用。我们的数据表明，MDA-7 蛋白可以在正常黑色素细胞和早期黑色素瘤中找到。在皮肤的平滑肌细胞中也观察到它。然而，为了与可能的肿瘤抑制作用相一致，MDA-7 表达在更晚期的黑色素瘤中降低，在转移性疾病中几乎检测不到水平。我们还在体外研究了过表达 MDA-7 对人黑色素瘤细胞的抗肿瘤作用。我们的结果表明，Ad-mda-7 会诱导黑色素瘤细胞凋亡和 G2/M 细胞周期停滞，但不会诱导正常人黑色素细胞。 (C) 2001 Wiley-Liss, Inc.
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. (C) 2001 Wiley-Liss, Inc.