Basu H S, Dreckschmidt N, Tu L, Chanbusarakum L
The Department of Human Oncology, University of Wisconsin, Madison 53792, USA.
Cancer Chemother Pharmacol. 1999;43(4):336-40. doi: 10.1007/s002800050904.
The polyamine analog bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4) depletes cellular polyamines and inhibits malignant cell growth. We have previously shown that BE-4-4-4-4 inhibits nucleosome condensation on supercoiled DNA in a cell-free system. Here we sought to determine whether BE-4-4-4-4 inhibits nucleosome condensation in cells, and whether that effect alters the expression of specific genes.
We used the simian virus 40 (SV-40) minichromosome as a model system and studied the expression of the viral late genes. It is known that the SV-40 late genes are regulated by the steroid receptor elements that, in turn, control gene expression by altering nucleosomal organization.
We observed a more than six fold increase in SV-40 late gene expression in cells pretreated with BE-4-4-4-4 for 18 h. The polyamine analog bisethyl norspermine (BE-3-3-3), that does not affect nucleosomal condensation in cell free systems and has little effect on chromatin structure in cultured human tumor cells, had a negligible effect on SV-40 late gene expression under treatment conditions identical to those used with BE-4-4-4-4.
Similar to the findings in the cell-free system, the polyamine analog BE-4-4-4-4 inhibited nucleosome formation and, thereby, altered the expression of specific genes in a cellular system.
多胺类似物双（乙氨基）-5,10,15-三氮杂十九烷（BE-4-4-4-4）可消耗细胞内的多胺并抑制恶性细胞生长。我们之前已经表明，BE-4-4-4-4在无细胞系统中可抑制超螺旋DNA上的核小体凝聚。在此，我们试图确定BE-4-4-4-4是否在细胞中抑制核小体凝聚，以及该效应是否会改变特定基因的表达。
我们使用猿猴病毒40（SV-40）微型染色体作为模型系统，并研究病毒晚期基因的表达。已知SV-40晚期基因受类固醇受体元件调控，而类固醇受体元件又通过改变核小体组织来控制基因表达。
我们观察到，用BE-4-4-4-4预处理18小时的细胞中，SV-40晚期基因表达增加了六倍多。多胺类似物双乙去甲精胺（BE-3-3-3）在无细胞系统中不影响核小体凝聚，并且对培养的人类肿瘤细胞中的染色质结构影响很小，在与BE-4-4-4-4相同的处理条件下，它对SV-40晚期基因表达的影响可忽略不计。
与无细胞系统中的发现相似，多胺类似物BE-4-4-4-4抑制核小体形成，从而改变细胞系统中特定基因的表达。
