Reprogramming leukemia cells to terminal differentiation and growth arrest by RNA interference of PU.1
Reprogramming leukemia cells to terminal differentiation and growth arrest by RNA interference of PU.1
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DOI：
10.1158/1541-7786.mcr-07-0145
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发表时间：
2007-10-01
影响因子：
5.2
通讯作者：
Skoultchi, Arthur I.
中科院分区：
文献类型：
--
作者：
Papetti, Michael;Skoultchi, Arthur I.
恶性转化通常导致正常增殖控制的丧失和细胞分化的抑制。一些肿瘤细胞可以被刺激重新进入其分化程序并经历终末生长停滞。小鼠红白血病（MEL）细胞的体外分化是肿瘤细胞重编程的一个重要例子。MEL细胞是恶性成红细胞，其由于转录因子PU. 1的表达失调而被阻止分化成成熟RBC，所述转录因子PU. 1结合并抑制加塔-1，即红细胞减少的主要转录调节因子。我们使用RNA干扰来询问抑制PU.1合成是否足以导致MEL细胞丧失其恶性特性。我们在这里报告说，MEL细胞与PU.1特异性短干扰RNA寡核苷酸转染导致细胞恢复红系分化，积累血红蛋白，并进行终端生长停滞。针对特异性、异常表达的转录因子的RNA干扰可能为开发其他血液恶性肿瘤的有效抗肿瘤疗法带来希望。
Malignant transformation often leads to both loss of normal proliferation control and inhibition of cell differentiation. Some tumor cells can be stimulated to reenter their differentiation program and to undergo terminal growth arrest. The in vitro differentiation of mouse erythroleukemia (MEL) cells is an important example of tumor cell reprogramming. MEL cells are malignant erythroblasts that are blocked from differentiating into mature RBC due to dysregulated expression of the transcription factor PU.1, which binds to and represses GATA-1, the major transcriptional regulator of erythropolesis. We used RNA interference to ask whether inhibiting PU.1 synthesis was sufficient to cause MEL cells to lose their malignant properties. We report here that transfection of MEL cells with a PU.1-specific short interfering RNA oligonucleotide causes the cells to resume erythroid differentiation, accumulate hemoglobin, and undergo terminal growth arrest. RNA interference directed at specific, aberrantly expressed transcription factors may hold promise for the development of potent antitumor therapies in other hematologic malignancies.