Malignant Progression in Human Melanoma

我们已经证实，多梳蛋白BMI-1在黑色素瘤细胞中的表达水平远远高于其良性对应的正常人类黑素细胞。这种高水平的表达显然在人类黑色素瘤组织中是保守的，并且经常在独特的点状核分布中发现。Bmi-1在人黑色素瘤细胞中的表达似乎是转录后调节的。我们已经开发出逆转录病毒和慢病毒载体，允许我们使用RNA干扰来降低Bmi-1在这些细胞中的表达。此外，我们已经制定并获得了一项动物方案的批准，该方案允许我们在体内评估BMI-1丢失对这些细胞的影响。我们扩大了这些研究的范围，包括使用微阵列分析来筛选其表达通过减少BMI-1表达而改变的功能基因组。此外，我们正在寻找其他多梳蛋白，如EZH2，以确定它们在黑色素瘤中的潜在作用，并利用表达工具启动功能获得方法来确定其在黑素细胞和黑色素瘤恶性进展中的作用。我们还计划利用批准的临床方案来分析BMI-1和其他相关蛋白在人类黑素细胞中的表达。

We have confirmed that the polycomb protein BMI-1 is expressed at much higher levels in melanoma cells than in their benign counterpart, normal human melanocytes. This high level of expression is apparently conserved in human melanoma tissue and often is found in a distinctive punctate nuclear distribution. Expression of BMI-1 in human melanoma cells appears to be post-transcriptionally regulated.We have developed retroviral and lentiviral vectors that permit us to reduce BMI-1 expression in these cells using RNA interference. Additionally, we have formulated and acquired approval of an animal protocol permitting us to assess the effects of BMI-1 loss in these cells in vivo. We have expanded the scope of these investigations to include the use of microarray analysis to screen for functional gene groups whose expression is modified by reduction of BMI-1 expression. Also, we are looking at other polycomb proteins, such as EZH2, for their potential role in melanoma and utilizing expression tools to initiate a gain-of-function approach to determining its role in melanocytes and melanoma malignant progression. We also plan to utilize an approved clinical protocol to analyze the expression of BMI-1 and other relevant proteins in human melanocytes.