• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Co-chaperone influence on androgen receptor signaling and identification of androgen receptor genes in prostate cancer.
【24h】

Co-chaperone influence on androgen receptor signaling and identification of androgen receptor genes in prostate cancer.

机译：伴侣伴侣对前列腺癌中雄激素受体信号传导和雄激素受体基因鉴定的影响。

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

The androgen receptor (AR) plays pivotal roles in the initiation and progression of prostate cancer, which is a major health burden worldwide. Initially, the disease is androgen-dependent and readily responds to androgen-ablation therapies. However, after a relatively short period of ablation therapy, the tumor returns as a more aggressive androgen-ablation resistant disease for which there are no effective therapies. Thus, the detection of prostate cancer at an early curable stage, as well as understanding the mechanisms of cancer progression are of utmost importance.; Though ablation-resistant prostate tumors often respond to alternate ablation therapies, eventually such tumors become refractile to all. This occurs not from a loss of AR, but rather the acquired ability of the AR to signal at subphysiologic levels of androgen. While various mechanisms have been proposed, the details and the relative contribution of each mechanism are poorly understood. The following thesis attempts to enhance our knowledge of progression to advanced prostate cancer by examining an upstream factor as well as downstream effectors of AR signaling.; AR activation requires the proper high ligand-binding affinity conformation assembled by molecular chaperones to unfold and maintain accessibility to the ligand-binding pocket. The core complex of molecular chaperones are assisted and regulated by accessory proteins, including TPR-containing proteins. In collaboration with Dr. Wayne Tilley's group (Adelaide, Australia), we were able to demonstrate modulation of AR function by a novel TPR-containing protein, alphaSGT. The effect appeared to be the result of an influence on nuclear translocation.; With a relatively small number of known AR-regulated genes, it is difficult to understand the biological effects of AR signaling in normal, let alone advanced prostate tumors. Using ChIP Display, we identified several new AR binding sites, which were in the vicinity of androgen-regulated genes. A subset of genes was repressed upon androgen-treatment, a group that has been largely ignored. Our findings provide novel targets for the study of AR function in prostate cancer.
机译：雄激素受体（AR）在前列腺癌的发生和发展中起着关键作用，而前列腺癌是全世界的主要健康负担。最初，该疾病是雄激素依赖性的，并且容易对雄激素消融疗法产生反应。然而，在相对较短的消融治疗期后，肿瘤会以更具侵略性的雄激素消融抵抗性疾病的形式复发，目前尚无有效的治疗方法。因此，在可治愈的早期阶段检测前列腺癌以及了解癌症进展的机制至关重要。尽管抗消融的前列腺肿瘤经常对替代的消融疗法产生反应，但最终这些肿瘤对所有人都具有屈光性。这不是由于AR的丧失而发生的，而是由于AR在亚生理水平的雄激素水平上发出信号所获得的能力。虽然已经提出了各种机制，但是对每种机制的细节和相对贡献知之甚少。以下论文试图通过研究AR信号传导的上游因子和下游效应子来增强我们对晚期前列腺癌进展的认识。 AR激活需要分子伴侣组装的适当的高配体结合亲和力构象，以展开并保持对配体结合口袋的可及性。分子伴侣的核心复合物由辅助蛋白（包括含TPR的蛋白）协助和调节。与Wayne Tilley博士的小组（澳大利亚阿德莱德）合作，我们能够证明一种新型的含TPR的蛋白质alphaSGT对AR功能的调节作用。这种作用似乎是对核易位的影响的结果。由于已知的AR调节基因数量相对较少，因此难以理解AR信号在正常前列腺癌（更不用说晚期前列腺癌）中的生物学作用。使用ChIP Display，我们确定了几个新的AR结合位点，它们位于雄激素调节基因附近。基因的一个子集在雄激素处理后被抑制，这一组在很大程度上被忽略了。我们的发现为前列腺癌AR功能的研究提供了新的靶点。

著录项

  • 作者

    Prescott, Jennifer.;

  • 作者单位

    University of Southern California.$bPreventive Medicine.;

  • 授予单位 University of Southern California.$bPreventive Medicine.;
  • 学科 Biology Molecular.; Health Sciences Epidemiology.
  • 学位 Ph.D.
  • 年度 2007
  • 页码 163 p.
  • 总页数 163
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子遗传学;
  • 关键词

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