• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Genes and Development: a Journal Devoted to the Molecular Analysis of Gene Expression in Eukaryotes, Prokaryotes, and Viruses >ETV1 directs androgen metabolism and confers aggressive prostate cancer in targeted mice and patients
【24h】

ETV1 directs androgen metabolism and confers aggressive prostate cancer in targeted mice and patients

机译：ETV1指导雄激素代谢并赋予目标小鼠和患者侵袭性前列腺癌

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Distinguishing aggressive from indolent disease and developing effective therapy for advanced disease are the major challenges in prostate cancer research. Chromosomal rearrangements involving ETS transcription factors, such as ERG and ETV1, occur frequently hi prostate cancer. How they contribute to tumorigenesis and whether they play similar or distinct in vivo roles remain elusive. Here we show that in mice with ERG or ETV1 targeted to the endogenous Tmprss2 locus, either factor cooperated with loss of a single copy of Pten, leading to localized cancer, but only ETV1 appeared to support development of invasive adenocarcinoma under the background of full Pten loss. Mechanistic studies demonstrated that ERG and ETV1 control a common transcriptional network but largely in an opposing fashion. In particular, while ERG negatively regulates the androgen receptor (AR) transcriptional program, ETV1 cooperates with AR signaling by favoring activation of the AR transcriptional program. Furthermore, we found that ETV1 expression, but not that of ERG, promotes autonomous testosterone production. Last, we confirmed the association of an ETV1 expression signature with aggressive disease and poorer outcome in patient data. The distinct biology of ETVl-associated prostate cancer suggests that this disease class may require new therapies directed to underlying programs controlled by ETV1.
机译：在前列腺癌研究中，区分侵略性疾病与惰性疾病并开发针对晚期疾病的有效疗法是主要挑战。涉及ETS转录因子（例如ERG和ETV1）的染色体重排在前列腺癌中经常发生。它们如何促进肿瘤发生，以及它们在体内起着相似还是不同的作用仍然是未知的。在这里，我们显示，在具有针对内源性Tmprss2基因座的ERG或ETV1的小鼠中，任一因素都与单拷贝Pten的缺失协同作用，导致局部癌变，但只有ETV1似乎在全Pten的背景下支持浸润性腺癌的发展。失利。机理研究表明，ERG和ETV1控制着一个通用的转录网络，但是在很大程度上是相反的。特别是，虽然ERG负调节雄激素受体（AR）的转录程序，但ETV1通过促进AR转录程序的激活而与AR信号传导协同作用。此外，我们发现ETV1表达而非ERG表达可促进自主睾丸激素的产生。最后，我们证实了ETV1表达特征与侵袭性疾病和较差的患者数据关联。与ETV1相关的前列腺癌的独特生物学特性表明，该疾病类别可能需要针对ETV1控制的基础程序的新疗法。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号