Androgen receptor signalling confers clonogenic and migratory advantages in urothelial cell carcinoma of the bladder.
Androgen receptor signalling confers clonogenic and migratory advantages in urothelial cell carcinoma of the bladder.
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DOI：
10.1002/1878-0261.12957
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发表时间：
2021-07
影响因子：
6.6
通讯作者：
Schalken JA
中科院分区：
文献类型：
--
作者：
Luna-Velez MV;Dijkstra JJ;Heuschkel MA;Smit FP;van de Zande G;Smeets D;Sedelaar JPM;Vermeulen M;Verhaegh GW;Schalken JA
膀胱尿路上皮细胞癌（UCC）的发病率在男性中约为女性的三倍。有几个迹象表明激素因素参与UCC的病因。在此，我们提供了雄激素信号在UCC进展中的证据。微阵列和qPCR分析显示，雄激素受体（AR）mRNA水平在UCC病例的子集中上调。在AR阳性UCC衍生细胞系模型UM-UC-3-AR中，雄激素处理增加了克隆形成能力，诱导形成大的干细胞样全克隆，而AR敲除或AR拮抗剂Enzalutamide处理消除了这种克隆形成优势。此外，AR信号传导的阻断降低了雄激素刺激的UM-UC-3-AR细胞的细胞迁移潜力。这些表型变化伴随着转录组的重新连接，其中近300个基因受到雄激素的差异调节，其中一些与两个独立数据集中UCC患者的AR表达相关。我们的研究结果表明，UCC中的AR信号有利于侵袭性表型的发展，并突出了其作为膀胱癌治疗靶点的潜力。激素因素与尿路上皮细胞癌（UCC）的病因有关。在此，我们探讨了雄激素受体（AR）信号在UCC进展中的作用。我们在UCC患者的一个子集中检测到AR表达。雄激素治疗增加了UCC衍生细胞系的克隆形成和迁移，而AR阻断则逆转了这些作用。最后，雄激素调节了近300个基因的表达，其中一些与UCC肿瘤组织中的AR表达相关。
Bladder urothelial cell carcinoma (UCC) incidence is about three times higher in men compared with women. There are several indications for the involvement of hormonal factors in the aetiology of UCC. Here, we provide evidence of androgen signalling in UCC progression. Microarray and qPCR analysis revealed that the androgen receptor (AR) mRNA level is upregulated in a subset of UCC cases. In an AR‐positive UCC‐derived cell line model, UM‐UC‐3‐AR, androgen treatment increased clonogenic capacity inducing the formation of big stem cell‐like holoclones, while AR knockdown or treatment with the AR antagonist enzalutamide abrogated this clonogenic advantage. Additionally, blockage of AR signalling reduced the cell migration potential of androgen‐stimulated UM‐UC‐3‐AR cells. These phenotypic changes were accompanied by a rewiring of the transcriptome with almost 300 genes being differentially regulated by androgens, some of which correlated with AR expression in UCC patients in two independent data sets. Our results demonstrate that AR signals in UCC favouring the development of an aggressive phenotype and highlights its potential as a therapeutic target for bladder cancer. Hormonal factors have been implicated in the aetiology of urothelial cell carcinoma (UCC). Here, we explored the role of androgen receptor (AR) signalling in UCC progression. We detected AR expression in a subset of patients with UCC. Androgen treatment increased clonogenicity and migration of a UCC‐derived cell line, while AR blockade reverted these effects. Finally, androgens regulated the expression of nearly 300 genes, some of which correlated with AR expression in UCC tumour tissues.
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影响因子：
11.2
作者：
Coma S;Amin DN;Shimizu A;Lasorella A;Iavarone A;Klagsbrun M
通讯作者：
Klagsbrun M
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
4.2
作者：
Cheng, Honglin;Hao, Yanni;Wu, Xiaohou
通讯作者：
Wu, Xiaohou
影响因子：
2.1
作者：
ARIEL, I;LUSTIG, O;HOCHBERG, A
通讯作者：
HOCHBERG, A