Interaction between AR signalling and CRKL bypasses casodex inhibition in prostate cancer

Reebye V.; Bevan C.L.; Nohadani M.; Hajitou A.; Habib N.A.; Mintz P.J.

首页> 外文期刊>Cellular Signalling >Interaction between AR signalling and CRKL bypasses casodex inhibition in prostate cancer

【24h】

Interaction between AR signalling and CRKL bypasses casodex inhibition in prostate cancer

机译：AR信号传导与CRKL之间的相互作用绕过前列腺癌对cadex的抑制作用

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相似文献
相关主题

摘要

The underlying mechanism of failed androgen ablation therapy is unknown. It is recognised that under therapeutic conditions the androgen receptor (AR) remains functionally active independent of hormone stimulation and may function through an alternative pathway. We report a novel cooperative interaction between CRKL (an intracellular signalling adaptor protein) and the AR. We demonstrate by biochemical and genetic approaches that CRKL is associated with the AR complex and is localised in the nucleus of prostate cancer cells and patient tissue biopsies. The interaction between CRKL and the AR is functionally relevant as demonstrated by its presence on the enhancer region of an androgen regulated gene (human Kallikrein-2), its upregulation of PSA, and reduction in AR transactivation following its disruption by siRNA knockdown. In the presence of the AR inhibitor casodex, the expression of CRKL co-stimulated by growth factors is able to rescue AR activity independent of hormone. Our data provides insight on how a non-nuclear factor such as CRKL may interact with the AR complex to bypass hormone dependency by using an alternative growth factor signalling pathway in advanced prostate cancer.

机译：雄激素消融治疗失败的潜在机制尚不清楚。公认的是，在治疗条件下，雄激素受体（AR）保持功能独立于激素刺激，并可能通过其他途径起作用。我们报告CRKL（一种细胞内信号转导蛋白）和AR之间的新型合作相互作用。我们通过生化和遗传方法证明CRKL与AR复合物相关，并位于前列腺癌细胞和患者组织活检的细胞核中。 CRKL和AR之间的相互作用在功能上是相关的，如其在雄激素调节基因（人类激肽释放酶2）的增强子区域上的存在，其PSA的上调以及在被siRNA敲除破坏后AR反式激活的减少所证明。在AR抑制剂casodex的存在下，生长因子共同刺激的CRKL的表达能够拯救AR活性，而与激素无关。我们的数据提供了关于在晚期前列腺癌中使用替代生长因子信号传导途径的非核因子（如CRKL）如何与AR复合物相互作用以绕过激素依赖性的见解。

著录项

来源
《Cellular Signalling》 |2010年第12期|共8页
作者
Reebye V.; Bevan C.L.; Nohadani M.; Hajitou A.; Habib N.A.; Mintz P.J.;
展开▼
作者单位

展开▼
收录信息
原文格式 PDF
正文语种 eng
中图分类细胞形态学;
关键词
Androgen receptor; CRKL; Prostate cancer; Signal transduction;

机译：雄激素受体;CRKL;前列腺癌;信号转导;

相似文献

外文文献
中文文献
专利

1. Interaction between AR signalling and CRKL bypasses casodex inhibition in prostate cancer [J] . Reebye V., Bevan C.L., Nohadani M., Cellular Signalling . 2010,第12期

机译：AR信号传导与CRKL之间的相互作用绕过前列腺癌对cadex的抑制作用
2. ASC-J9 (R), and not Casodex or Enzalutamide, suppresses prostate cancer stem/progenitor cell invasion via altering the EZH2-STAT3 signals [J] . Wen Simeng, Tian Jing, Niu Yuanjie, Cancer letters . 2016,第2期

机译：ASC-J9（R），而不是Casodex或Enzalutamide，通过改变EZH2-STAT3信号抑制前列腺癌干/祖细胞的侵袭
3. Anti-androgen receptor ASC-J9 versus anti-androgens MDV3100 (Enzalutamide) or Casodex (Bicalutamide) leads to opposite effects on prostate cancer metastasis via differential modulation of macrophage infiltration and STAT3-CCL2 signaling [J] . T-H Lin, K Izumi, S O Lee, Cell death & disease. . 2013,第8期

机译：抗雄激素受体ASC-J9与抗雄激素MDV3100（Enzalutamide）或Casodex（比卡鲁胺）通过巨噬细胞浸润和STAT3-CCL2信号的差异调节对前列腺癌转移产生相反的影响
4. Identification of Common and Unique Susceptibility Pathways Among Cancers of the Lung, Breast, and Prostate from Genome-Wide Association Studies and Tissue-Specific Protein Interactions [C] . David C. Qian, Jinyoung Byun, Younghun Han, International Molecular Medicine Tri-Conference. . 2015

机译：从基因组 - 宽协会研究和组织特异性蛋白质相互作用鉴定肺癌，乳腺癌和前列腺癌中共同和独特的易感性途径
5. Characterization of FGFR Signaling in Prostate Cancer Stem Cells and Inhibition via TKI Treatment [D] . Ko, Juyeon. 2021

机译：前列腺癌干细胞中FGFR信号传导的表征及TKI治疗抑制作用
6. Undesirable Status of Prostate Cancer Cells after Intensive Inhibition of AR Signaling: Post-AR Era of CRPC Treatment [O] . Tomoyuki Makino, Kouji Izumi, Atsushi Mizokami 2021

机译：在AR信号传导抑制后前列腺癌细胞的不良状态：CRPC治疗后的AR时代
7. Stilbene induced inhibition of androgen receptor dimerization: implications for AR and ARΔLBD-signalling in human prostate cancer cells. [O] . Wolfgang Streicher, Manuel Luedeke, Anca Azoitei, 2014

机译：二苯乙烯诱导雄激素受体二聚化的抑制：对人前列腺癌细胞中aR和aRΔLBD-信号传导的影响。
8. Molecular Determinants of Prostate Cancer Progression Across Race- Ethnicity. Project A - The Human 5RD5A2 Gene and Prostate Cancer Progression. Project B - Androgen Receptor (AR) Signaling in Prostate Cancer Progression. Project C - Cellular and Molecular Markers of Prostate Cancer Progression Core - Epidemiology Core [R] . Ross, R. R. , Reichardt, J. , Coetzee, G. A. , 2002

机译：跨越种族的前列腺癌进展的分子决定因素。项目a - 人类5RD5a2基因和前列腺癌进展。项目B - 雄激素受体（aR）在前列腺癌进展中的信号传导。项目C - 前列腺癌进展核心的细胞和分子标记 - 流行病学核心

Interaction between AR signalling and CRKL bypasses casodex inhibition in prostate cancer

摘要

著录项

相似文献

相关主题

期刊订阅