Constitutively active androgen receptor splice variants AR-V3, AR-V7 and AR-V9 are co-expressed in castration-resistant prostate cancer metastases.
Constitutively active androgen receptor splice variants AR-V3, AR-V7 and AR-V9 are co-expressed in castration-resistant prostate cancer metastases.
复制标题
组成型活性雄激素受体剪接变体AR-V3，AR-V7和AR-V9在castration抗性的前列腺癌转移中共表达。
DOI：
10.1038/s41416-018-0172-0
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发表时间：
2018-08
影响因子：
8.8
通讯作者：
Visakorpi T
中科院分区：
文献类型：
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作者：
Kallio HML;Hieta R;Latonen L;Brofeldt A;Annala M;Kivinummi K;Tammela TL;Nykter M;Isaacs WB;Lilja HG;Bova GS;Visakorpi T
前列腺癌(PC)患者中有相当一部分患有去势抵抗型前列腺癌(CRPC)，他们对针对CRPC开发的雄激素受体(AR)靶向药物表现出主要的耐药性。由于一种解释可能是结构性活性雄激素受体剪接变异体(AR-vs)的表达，我们目前的目标是研究AR-vs和其他AR异常，以更好地了解CRPC的出现。我们对前列腺癌不同阶段的标本进行了下一代测序和免疫组织化学分析。仅在CRPC标本中检测到AR突变和拷贝数变异。在30例转移性CRPC患者中有5例观察到AR的基因组结构重排，但与已知的AR-vs的表达无关。AR-V主要为AR-V3、AR-V7和AR-V9，在CRPC中的表达水平显著高于前列腺癌标本。在25例表达AR变异体的CRPC转移癌中，17例同时表达这3种AR-V。AR-V7蛋白在CRPC中的表达具有高度的异质性，与激素单纯的肿瘤相比，其表达水平更高。AR-V3、AR-V7和AR-V9在CRPC转移瘤中共表达，突出了这样一个事实，即通过所有AR-V的共同区域抑制AR功能可能为CRPC患者提供额外的好处。
A significant subset of prostate cancer (PC) patients with a castration-resistant form of the disease (CRPC) show primary resistance to androgen receptor (AR)-targeting drugs developed against CRPC. As one explanation could be the expression of constitutively active androgen receptor splice variants (AR-Vs), our current objectives were to study AR-Vs and other AR aberrations to better understand the emergence of CRPC. We analysed specimens from different stages of prostate cancer by next-generation sequencing and immunohistochemistry. AR mutations and copy number variations were detected only in CRPC specimens. Genomic structural rearrangements of AR were observed in 5/30 metastatic CRPC patients, but they were not associated with expression of previously known AR-Vs. The predominant AR-Vs detected were AR-V3, AR-V7 and AR-V9, with the expression levels being significantly higher in CRPC cases compared to prostatectomy samples. Out of 25 CRPC metastases that expressed any AR variant, 17 cases harboured expression of all three of these AR-Vs. AR-V7 protein expression was highly heterogeneous and higher in CRPC compared to hormone-naïve tumours. AR-V3, AR-V7 and AR-V9 are co-expressed in CRPC metastases highlighting the fact that inhibiting AR function via regions common to all AR-Vs is likely to provide additional benefit to patients with CRPC.
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DOI：
10.1158/1078-0432.ccr-17-0017
发表时间：
2017-08-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Kohli M;Ho Y;Hillman DW;Van Etten JL;Henzler C;Yang R;Sperger JM;Li Y;Tseng E;Hon T;Clark T;Tan W;Carlson RE;Wang L;Sicotte H;Thai H;Jimenez R;Huang H;Vedell PT;Eckloff BW;Quevedo JF;Pitot HC;Costello BA;Jen J;Wieben ED;Silverstein KAT;Lang JM;Wang L;Dehm SM
通讯作者：
Dehm SM
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
2
作者：
Eisermann K;Wang D;Jing Y;Pascal LE;Wang Z
通讯作者：
Wang Z
影响因子：
23.4
作者：
De laere, Bram;van Dam, Pieter-Jan;Lindberg, Johan
通讯作者：
Lindberg, Johan
影响因子：
16.6
作者：
通讯作者：
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