• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国政府科技报告 >Mitogen-Induced Transactivation of the Androgen Receptor as a Mechanism for Recurrent Prostate Cancer Development
【24h】

Mitogen-Induced Transactivation of the Androgen Receptor as a Mechanism for Recurrent Prostate Cancer Development

机译：丝裂原诱导的雄激素受体反式激活作为复发性前列腺癌发生的机制

获取原文
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The androgen receptor (AR) is required for normal prostate development and the onset and progression of prostate cancer. AR has the modular structure characteristic of steroid hormone receptors, with an NH2- terminal transcriptional activation domain, conserved DNA binding domain, hinge region and carboxyl-terminal ligand binding domain (1, 2). AR mediates the biological effects of androgens by binding testosterone and dihydrotestosterone (DHT) with high affinity (3). Androgen binding in the ligand binding domain stabilizes AR through the NH2- and carboxyl-terminal N/C interaction that increases AR transcriptional activity (4). Androgen deprivation by surgical or chemical castration to treat advanced prostate cancer reduces AR transcriptional activity and promotes tumor regression. Several mechanisms have been proposed to explain the emergence of castration-recurrent prostate cancer after androgen deprivation therapy (reviewed in ref. 5). AR transcriptional activity and CWR-R1 human prostate cancer cell proliferation are hypersensitive to DHT (6). AR localizes in nuclei of prostate cancer cells despite low levels of circulating androgen and appears to mediate recurrent growth after androgen deprivation (7). This could be explained by the presence of sufficient testosterone or DHT to activate AR in the microenvironment of castration- recurrent prostate cancer tissue (8, 9). On the other hand, cell culture studies suggest that AR transcriptional activity involves growth factor signaling under conditions of androgen deprivation. HER2/neu, keratinocyte growth factor, insulin-like growth factor-1 and Il-6 have been reported to activate AR in the absence of androgen (10-12). Epidermal growth factor (EGF) dependent phosphorylation of transcriptional intermediary factor 2 and heregulin signaling through the HER2 and HER3 tyrosine kinases increase AR transactivation and alter the growth of CWR-R1 prostate cancer cells in response to low levels of androgen (13, 14).

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