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首页> 外文期刊>Cancer Cell >TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer
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TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer

机译：Trim24是前列腺癌中的致癌转录活化剂

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摘要

Androgen receptor (AR) signaling is a key driver of prostate cancer (PC). While androgen-deprivation therapy is transiently effective in advanced disease, tumors often progress to a lethal castration-resistant state (CRPC). We show that recurrent PC-driver mutations in speckle-type POZ protein (SPOP) stabilize the TRIM24 protein, which promotes proliferation under low androgen conditions. TRIM24 augments AR signaling, and AR and TRIM24 co-activated genes are significantly upregulated in CRPC. Expression of TRIM24 protein increases from primary PC to CRPC, and both TRIM24 protein levels and the AR/TRIM24 gene signature predict disease recurrence. Analyses in CRPC cells reveal that the TRIM24 bromodomain and the AR-interacting motif are essential to support proliferation. These data provide a rationale for therapeutic TRIM24 targeting in SPOP mutant and CRPC patients.
机译：雄激素受体（AR）信号传导是前列腺癌（PC）的关键驱动力。 虽然雄激素剥夺治疗在晚期疾病中瞬时有效，但肿瘤往往进入致命的抗阉割状态（CRPC）。 我们表明，斑点型POZ蛋白（SPOP）中的复发性PC驱动突变稳定了Trim24蛋白，其在低雄激素条件下促进增殖。 Trim24增强AR信号传导和AR和TRIM24共激活基因在CRPC中显着上调。 TRIM24蛋白的表达从原发性PC增加到CRPC，以及TRIM24蛋白水平和AR / TREM24基因签名预测疾病复发。 CRPC细胞中的分析揭示了Trim24溴和Ar相互作用基序对于支持增殖是必不可少的。 这些数据提供了在孢子突变体和CRPC患者中靶向治疗饰边24的理由。

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  • 来源
    《Cancer Cell》 |2016年第6期|共13页
  • 作者

    Groner Anna C.; Cato Laura; de Tribolet-Hardy Jonas; Bernasocchi Tiziano; Janouskova Hana; Melchers Diana; Houtman Rene; Cato Andrew C. B.; Tschopp Patrick; Gu Lei; Corsinotti Andrea; Zhong Qing; Fankhauser Christian; Fritz Christine; Poyet Cedric; Wagner Ulrich; Guo Tiannan; Aebersold Ruedi; Garraway Levi A.; Wild Peter J.; Theurillat Jean-Philippe; Brown Myles;

  • 作者单位

    Harvard Univ Sch Med Dana Farber Canc Inst Dept Med Oncol 44 Binney St Boston MA 02115 USA;

    Harvard Univ Sch Med Dana Farber Canc Inst Dept Med Oncol 44 Binney St Boston MA 02115 USA;

    Harvard Univ Sch Med Dana Farber Canc Inst Dept Med Oncol 44 Binney St Boston MA 02115 USA;

    Inst Oncol Res CH-6500 Bellinzona Switzerland;

    Inst Oncol Res CH-6500 Bellinzona Switzerland;

    PamGene Int NL-5211 HH Den Bosch Netherlands;

    PamGene Int NL-5211 HH Den Bosch Netherlands;

    Karlsruhe Inst Technol Inst Toxicol &

    Genet D-76344 Eggenstein Leopoldshafen Germany;

    Harvard Univ Sch Med Dept Genet Boston MA 02215 USA;

    Harvard Univ Sch Med Childrens Hosp Boston Div Newborn Med Boston MA 02215 USA;

    Univ Edinburgh Sch Biol Sci Inst Stem Cell Res MRC Ctr Regenerat Med Edinburgh EH16 4UU;

    Univ Zurich Hosp Inst Surg Pathol CH-8091 Zurich Switzerland;

    Univ Zurich Hosp Inst Surg Pathol CH-8091 Zurich Switzerland;

    Univ Zurich Hosp Inst Surg Pathol CH-8091 Zurich Switzerland;

    Univ Zurich Hosp Dept Urol CH-8091 Zurich Switzerland;

    Univ Zurich Hosp Inst Surg Pathol CH-8091 Zurich Switzerland;

    ETH Inst Mol Syst Biol Dept Biol CH-8093 Zurich Switzerland;

    ETH Inst Mol Syst Biol Dept Biol CH-8093 Zurich Switzerland;

    Harvard Univ Sch Med Dana Farber Canc Inst Dept Med Oncol 44 Binney St Boston MA 02115 USA;

    Univ Zurich Hosp Inst Surg Pathol CH-8091 Zurich Switzerland;

    Inst Oncol Res CH-6500 Bellinzona Switzerland;

    Harvard Univ Sch Med Dana Farber Canc Inst Dept Med Oncol 44 Binney St Boston MA 02115 USA;

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  • 正文语种 eng
  • 中图分类 肿瘤学;
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