Functional characterization of ATAD2 as a new cancer/testis factor and a predictor of poor prognosis in breast and lung cancers
Functional characterization of ATAD2 as a new cancer/testis factor and a predictor of poor prognosis in breast and lung cancers
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DOI：
10.1038/onc.2010.259
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发表时间：
2010-09-01
期刊：
影响因子：
8
通讯作者：
Khochbin, S.
中科院分区：
文献类型：
--
作者：
Caron, C.;Lestrat, C.;Khochbin, S.
癌细胞经常表达通常在男性生殖细胞中活跃的基因。ATAD2是其中一种编码保守因子，包含AAA型atp酶结构域和溴结构域。我们在这里表明，ATAD2在睾丸和许多不同起源的癌症中都是高表达的，它的高表达是肺癌和乳腺癌快速死亡的一个强有力的预测因子。这些观察结果表明，ATAD2作用于上游和基本细胞过程，促进多种不相关细胞类型的肿瘤发生。因此，我们的功能研究表明ATAD2控制染色质动力学，基因组转录活性和凋亡细胞反应。我们还可以强调其两个调节结构域的一些重要的内在特性，包括AAA atp酶结构域和溴结构域之间的功能串扰。总之，这些数据表明ATAD2在体细胞中的过表达，通过作用于染色质的基本特性，可能有助于恶性转化。中华肿瘤杂志（2010）29,571 - 581；doi: 10.1038 / onc.2010.259;2010年6月28日在线发布
Cancer cells frequently express genes normally active in male germ cells. ATAD2 is one of them encoding a conserved factor harbouring an AAA type ATPase domain and a bromodomain. We show here that ATAD2 is highly expressed in testis as well as in many cancers of different origins and that its high expression is a strong predictor of rapid mortality in lung and breast cancers. These observations suggest that ATAD2 acts on upstream and basic cellular processes to enhance oncogenesis in a variety of unrelated cell types. Accordingly, our functional studies show that ATAD2 controls chromatin dynamics, genome transcriptional activities and apoptotic cell response. We could also highlight some of the important intrinsic properties of its two regulatory domains, including a functional cross-talk between the AAA ATPase domain and the bromodomain. Altogether, these data indicate that ATAD2 overexpression in somatic cells, by acting on basic properties of chromatin, may contribute to malignant transformation. Oncogene (2010) 29, 5171-5181; doi:10.1038/onc.2010.259; published online 28 June 2010