Malignant Progression in Human Melanoma

人类黑色素瘤的恶性进展

• 批准号: 7338697
• 负责人: thomas j hornyak
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7338697
• 关键词: Malignant; Progression; Human; Melanoma

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.

我们已经证实，在黑色素瘤细胞中，多角膜蛋白BMI-1的表达比其良性对应的正常人黑色素细胞在更高的水平上。这种高水平的表达显然是在人类黑色素瘤组织中保守的，并且经常在特殊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在转录后调节的。我们开发了逆转录病毒和慢病毒载体，使我们能够使用RNA干扰来降低这些细胞中的BMI-1表达。此外，我们已经制定并获得了动物方案的批准，允许我们评估这些在体内这些细胞中BMI-1损失的影响。我们已经扩大了这些研究的范围，以包括使用微阵列分析来筛选功能基因组，这些功能基因组通过降低BMI-1表达来改变其表达。同样，我们正在研究其他多肉蛋白，例如EZH2，以实现它们在黑色素瘤中的潜在作用，并利用表达工具来启动功能奖励方法来确定其在黑素细胞和黑色素瘤恶性进展中的作用。我们还计划利用经过认可的临床方案来分析人类黑色素细胞中BMI-1和其他相关蛋白的表达。