Androgen receptor signalling confers clonogenic and migratory advantages in urothelial cell carcinoma of the bladder
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 r...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-07-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.12957 |
| _version_ | 1818624043349180416 |
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| author | Maria V. Luna‐Velez Jelmer J. Dijkstra Marina A. Heuschkel Frank P. Smit Guillaume van de Zande Dominique Smeets J. P. Michiel Sedelaar Michiel Vermeulen Gerald W. Verhaegh Jack A. Schalken |
| author_facet | Maria V. Luna‐Velez Jelmer J. Dijkstra Marina A. Heuschkel Frank P. Smit Guillaume van de Zande Dominique Smeets J. P. Michiel Sedelaar Michiel Vermeulen Gerald W. Verhaegh Jack A. Schalken |
| author_sort | Maria V. Luna‐Velez |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T18:50:41Z |
| format | Article |
| id | doaj.art-232b1f170c384ea19e66163c0f81904f |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-12-16T18:50:41Z |
| publishDate | 2021-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-232b1f170c384ea19e66163c0f81904f2022-12-21T22:20:42ZengWileyMolecular Oncology1574-78911878-02612021-07-011571882190010.1002/1878-0261.12957Androgen receptor signalling confers clonogenic and migratory advantages in urothelial cell carcinoma of the bladderMaria V. Luna‐Velez0Jelmer J. Dijkstra1Marina A. Heuschkel2Frank P. Smit3Guillaume van de Zande4Dominique Smeets5J. P. Michiel Sedelaar6Michiel Vermeulen7Gerald W. Verhaegh8Jack A. Schalken9Department of Urology Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen the NetherlandsDepartment of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute Radboud University Nijmegen the NetherlandsDepartment of Urology Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen the NetherlandsMDxHealth Nijmegen the NetherlandsDepartment of Genetics Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen the NetherlandsDepartment of Genetics Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen the NetherlandsDepartment of Urology Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen the NetherlandsDepartment of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute Radboud University Nijmegen the NetherlandsDepartment of Urology Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen the NetherlandsDepartment of Urology Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen the NetherlandsBladder 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.https://doi.org/10.1002/1878-0261.12957androgen deprivation therapyandrogen receptorcell migrationcolony formationtranscriptome analysisurothelial cell carcinoma |
| spellingShingle | Maria V. Luna‐Velez Jelmer J. Dijkstra Marina A. Heuschkel Frank P. Smit Guillaume van de Zande Dominique Smeets J. P. Michiel Sedelaar Michiel Vermeulen Gerald W. Verhaegh Jack A. Schalken Androgen receptor signalling confers clonogenic and migratory advantages in urothelial cell carcinoma of the bladder Molecular Oncology androgen deprivation therapy androgen receptor cell migration colony formation transcriptome analysis urothelial cell carcinoma |
| title | Androgen receptor signalling confers clonogenic and migratory advantages in urothelial cell carcinoma of the bladder |
| title_full | Androgen receptor signalling confers clonogenic and migratory advantages in urothelial cell carcinoma of the bladder |
| title_fullStr | Androgen receptor signalling confers clonogenic and migratory advantages in urothelial cell carcinoma of the bladder |
| title_full_unstemmed | Androgen receptor signalling confers clonogenic and migratory advantages in urothelial cell carcinoma of the bladder |
| title_short | Androgen receptor signalling confers clonogenic and migratory advantages in urothelial cell carcinoma of the bladder |
| title_sort | androgen receptor signalling confers clonogenic and migratory advantages in urothelial cell carcinoma of the bladder |
| topic | androgen deprivation therapy androgen receptor cell migration colony formation transcriptome analysis urothelial cell carcinoma |
| url | https://doi.org/10.1002/1878-0261.12957 |
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