ERG is specifically associated with ETS-2 and ETV-4, but not with ETS-1, in prostate cancer.
ERG is specifically associated with ETS-2 and ETV-4, but not with ETS-1, in prostate cancer.
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DOI：
10.3892/ijmm.2012.1097
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发表时间：
2012-11
影响因子：
5.4
通讯作者：
Wernert N
中科院分区：
文献类型：
--
作者：
Adler D;Ochsenfahrt J;Fuchs K;Kristiansen G;Perner S;Wernert N
红母细胞转化特异性（ETS）转录因子家族在生理和病理条件中都起着重要作用。尽管许多研究都集中在单一组织和特定启动子背景下的单一ETS因子，但尚未研究特定细胞类型中存在的多个ETS成员的功能影响，特别是在前列腺癌（PCa）中。由于PCa中最突出的基因重排导致ETS相关基因（ERG）的过表达，本研究的目的是研究ERG是否是涉及其他ETS因素的复杂综合转录网络的一部分。更具体地说，由于ETS家族由27个成员组成，我们最初的工作重点是调查ERG是否与三个家族成员（ETS-1、ETS-2和ETS变体基因4 (ETV-4)）有关，作为PCa的原理证明。通过western blot分析，我们发现ERG、ETS-1、ETS-2和ETV-4在PC3细胞核提取物和人前列腺癌标本的蛋白裂解物中表达。使用抗erg抗体的免疫沉淀与PC3细胞核提取物以及从5名患者的PCa组织样本中制备的混合蛋白裂解液样品一起使用。重要的是，我们的研究结果显示，在PC3细胞核提取物和PCa组织蛋白裂解物中，ERG与ETS-2和ETV-4特异性相关，而与ETS-1无关。我们的研究结果有力地支持了这一观点，即ERG是一个复杂的综合转录网络的一部分，该转录网络涉及其他ETS因素，这些因素可能在PCa中合作或影响ERG的活性。与ERG相关的多个ETS因子在PCa中的功能影响需要进一步研究，因为它可能提供ERG在PCa中发挥其影响的机制，并可能随后有助于我们理解PCa的分子基础。
The erythroblast transformation-specific (ETS) family of transcription factors plays important roles in both physiological and pathological conditions. Even though many studies have focused on single ETS factors within a single tissue and within the context of specific promoters, the functional impact of multiple ETS members present within a specific cell type has not yet been investigated, especially in prostate cancer (PCa). As the most prominent gene rearrangement in PCa leads to the overexpression of the ETS-related gene (ERG), the aim of this study was to investigate whether ERG is part of a complex integrated transcriptional network that involves other ETS factors. More specifically, as the ETS family consists of 27 members, we focused our efforts initially on investigating whether ERG is associated with the three family members, ETS-1, ETS-2 and ETS variant gene-4 (ETV-4), in PCa as a proof of principle. Using western blot analysis, we show that ERG, ETS-1, ETS-2 and ETV-4 are expressed in PC3 cell nuclear extracts and in protein lysates prepared from human PCa prostatectomy specimens. Immunoprecipitations using an anti-ERG antibody were used with PC3 cell nuclear extracts as well as with a pooled protein lysate sample prepared from the PCa tissue samples of five patients. Importantly, our results revealed that ERG is specifically associated with ETS-2 and ETV-4, but not with ETS-1, in PC3 cell nuclear extracts and PCa tissue protein lysates. Our findings strongly support the notion that ERG is part of a complex integrated transcriptional network that involves other ETS factors, which are likely to cooperate or influence the activity of ERG in PCa. The functional impact of multiple ETS factors being associated with ERG in PCa requires further study, as it may provide insights into the mechanism by which ERG exerts its influence in PCa and may subsequently contribute to our understanding of the molecular basis of PCa.
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影响因子：
37.8
作者：
Hashiya, N;Jo, N;Morishita, R
通讯作者：
Morishita, R
影响因子：
8
作者：
Hahne, JC;Okuducu, AF;Wernert, N
通讯作者：
Wernert, N
影响因子：
8
作者：
Sementchenko, VI;Schweinfest, CW;Watson, DK
通讯作者：
Watson, DK
影响因子：
3.3
作者：
Guo CC;Dancer JY;Wang Y;Aparicio A;Navone NM;Troncoso P;Czerniak BA
通讯作者：
Czerniak BA
影响因子：
10.5
作者：
Hollenhorst, Peter C.;Shah, Atul A.;Graves, Barbara J.
通讯作者：
Graves, Barbara J.