DEK expression is controlled by E2F and deregulated in diverse tumor types
DEK expression is controlled by E2F and deregulated in diverse tumor types
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DOI：
10.4161/cc.5.11.2801
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发表时间：
2006-06-01
期刊：
影响因子：
4.3
通讯作者：
Muller, Heiko
中科院分区：
文献类型：
--
作者：
Carro, Maria Stella;Spiga, Fabio Mario;Muller, Heiko
与E2F转录因子异常活性相关的视网膜母细胞瘤（pRB）肿瘤抑制通路的解除在人类癌症中经常被观察到。基于微阵列的分析揭示了pRB抑制肿瘤活性的大量潜在下游介质，包括DEK，一种在携带易位的急性髓性白血病（AML）患者亚群中发现的CAN的融合伴侣。本文报道DEK的表达受E2F转录因子的直接控制。染色质免疫沉淀实验表明，DEK启动子在体内与内源性E2F结合。DEK启动子被E2F反激活，E2F结合位点的突变消除了这种作用。通过组织微阵列分析研究了DEK在人类肿瘤中的表达水平。我们发现DEK在许多实体肿瘤中过表达，如结肠癌、喉癌、膀胱癌和黑色素瘤。
Deregulation of the retinoblastoma (pRB) tumor suppressor pathway associated with aberrant activity of E2F transcription factors is frequently observed in human cancer. Microarray based analyses have revealed a large number of potential downstream mediators of the tumor suppressing activity of pRB, including DEK, a fusion partner of CAN found in a subset of acute myeloid leukaemia (AML) patients carrying a (6; 9) translocation.Here we report that the expression of DEK is under direct control of E2F transcription factors. Chromatin immunoprecipitation assays show that the DEK promoter is bound by endogenous E2F in vivo. The DEK promoter is transactivated by E2F and mutation of E2F binding sites eliminates this effect. Expression levels of DEK in human tumors have been investigated by tissue micro array analysis. We find that DEK is overexpressed in many solid tumors such as colon cancer, larynx cancer, bladder cancer, and melanoma.