Regulation of alphaB-crystallin gene expression by the transcription factor Ets1 in breast cancer.
Regulation of alphaB-crystallin gene expression by the transcription factor Ets1 in breast cancer.
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DOI：
10.1007/s10549-009-0330-4
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发表时间：
2010-01
影响因子：
3.8
通讯作者：
Cryns, Vincent L.
中科院分区：
文献类型：
--
作者：
Bosman, Joshua D.;Yehiely, Fruma;Evans, Joseph R.;Cryns, Vincent L.
最近的研究表明，小的热休克蛋白α B-晶状体蛋白在预后不良的基底样乳腺肿瘤中表达，并可能有助于其侵袭性表型。然而，基底细胞样肿瘤中α B-晶状体蛋白表达失调的机制尚不清楚。利用生物信息学方法，我们在人α B-晶状体蛋白启动子中鉴定了原癌基因Ets 1的推定DNA结合基序，Ets 1是ETS转录因子家族的成员，在回文ETS结合位点（EBS）与DNA结合。在这里，我们证明，异位表达Ets 1激活α B-晶体蛋白启动子的EBS依赖性机制，并增加α B-晶体蛋白的蛋白水平，而沉默Ets 1降低α B-晶体蛋白启动子的活性和蛋白水平。染色质免疫沉淀分析表明，内源性Ets 1结合的α B-晶体蛋白启动子在基底样乳腺癌细胞在体内。对可获得的基因表达数据的询问显示，Ets 1在人类基底样乳腺肿瘤中表达，并且与较差的生存率相关。总的来说，我们的研究结果指出了基底样乳腺癌中致癌转录因子Ets 1和α B-晶体蛋白之间以前未被认识到的联系。
Recent studies indicate that the small heat shock protein αB-crystallin is expressed in poor prognosis basal-like breast tumors and likely contributes to their aggressive phenotype. However, the mechanisms underlying the deregulated expression of αB-crystallin in basal-like tumors are poorly understood. Using a bioinformatics approach, we identified a putative DNA binding motif in the human αB-crystallin promoter for the proto-oncogene Ets1, a member of the ETS transcription factor family that bind to DNA at palindromic ETS-binding sites (EBS). Here we demonstrate that ectopic expression of Ets1 activates the αB-crystallin promoter by an EBS-dependent mechanism and increases αB-crystallin protein levels, while silencing Ets1 reduces αB-crystallin promoter activity and protein levels. Chromatin immunoprecipitation analyses showed that endogenous Ets1 binds to the αB-crystallin promoter in basal-like breast cancer cells in vivo. Interrogation of publically available gene expression data revealed that Ets1 is expressed in human basal-like breast tumors and is associated with poor survival. Collectively, our results point to a previously unrecognized link between the oncogenic transcription factor Ets1 and αB-crystallin in basal-like breast cancer.
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影响因子：
3.8
作者：
Ivanov, Olga;Chen, Feng;Cryns, Vincent L.
通讯作者：
Cryns, Vincent L.
影响因子：
8
作者：
Hahne, JC;Okuducu, AF;Wernert, N
通讯作者：
Wernert, N
影响因子：
50.3
作者：
Richardson, AL;Wang, ZGC;Ganesan, S
通讯作者：
Ganesan, S
影响因子：
4.8
作者：
Somasundaram, T;Bhat, SP
通讯作者：
Bhat, SP
影响因子：
3.9
作者：
Doerwald, L;van Rheede, T;Lubsen, NH
通讯作者：
Lubsen, NH