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Dihydrotestosterone increases the risk of bladder cancer in men

Men are at a higher risk of developing bladder cancer than women. Although the urinary bladder is not regarded as an sex organ, it has the potential to respond to androgen signals. The mechanisms responsible for the gender differences remain unexplained. Androgen receptor (AR) after binding with 5α-...

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Autores principales: Gil, Dorota, Zarzycka, Marta, Dulińska-Litewka, Joanna, Ciołczyk-Wierzbicka, Dorota, Lekka, Małgorzata, Laidler, Piotr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Japan 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6570698/
https://www.ncbi.nlm.nih.gov/pubmed/31119584
http://dx.doi.org/10.1007/s13577-019-00255-3
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author Gil, Dorota
Zarzycka, Marta
Dulińska-Litewka, Joanna
Ciołczyk-Wierzbicka, Dorota
Lekka, Małgorzata
Laidler, Piotr
author_facet Gil, Dorota
Zarzycka, Marta
Dulińska-Litewka, Joanna
Ciołczyk-Wierzbicka, Dorota
Lekka, Małgorzata
Laidler, Piotr
author_sort Gil, Dorota
collection PubMed
description Men are at a higher risk of developing bladder cancer than women. Although the urinary bladder is not regarded as an sex organ, it has the potential to respond to androgen signals. The mechanisms responsible for the gender differences remain unexplained. Androgen receptor (AR) after binding with 5α-dihydrotestosteron (DHT) undergoes a conformational change and translocates to nucleus to induce transcriptional regulation of target genes. However androgen/AR signaling can also be activated by interacting with several signaling molecules and exert its non-genomic function. The aim of present study was to explain whether the progression of bladder cancer in men is dependent on androgen/AR signaling. Studies were carried out on human bladder cancer cell lines: HCV29, T24, HT1376 and HTB9. Bladder cancer cells were treated for 48 h with 10 nM DHT or not, with replacement after 24 h. Expression of cell signaling proteins, was analyzed using Western Blot and RT-PCR. Subcellular localization of protein was studied using the ProteoExtract Subcellular Proteome Extraction Kit and Western blot analysis. We showed that DHT treatment significantly increased AR expression in bladder cell line HCV29. We also observed DHT-mediated activation of Akt/GSK-3β signaling pathway which plays a central role in cancer progression. Presented results also show that androgen/AR signaling is implicated in phosphorylation of eIF4E which can promote epithelial–mesenchymal transition (EMT). We indicate that AR plays an essential role in bladder cancer progression in male patients. Therefore, androgen-activated AR signaling is an attractive regulatory target for the inhibition or prevention of bladder cancer incidence in men.
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spelling pubmed-65706982019-07-01 Dihydrotestosterone increases the risk of bladder cancer in men Gil, Dorota Zarzycka, Marta Dulińska-Litewka, Joanna Ciołczyk-Wierzbicka, Dorota Lekka, Małgorzata Laidler, Piotr Hum Cell Research Article Men are at a higher risk of developing bladder cancer than women. Although the urinary bladder is not regarded as an sex organ, it has the potential to respond to androgen signals. The mechanisms responsible for the gender differences remain unexplained. Androgen receptor (AR) after binding with 5α-dihydrotestosteron (DHT) undergoes a conformational change and translocates to nucleus to induce transcriptional regulation of target genes. However androgen/AR signaling can also be activated by interacting with several signaling molecules and exert its non-genomic function. The aim of present study was to explain whether the progression of bladder cancer in men is dependent on androgen/AR signaling. Studies were carried out on human bladder cancer cell lines: HCV29, T24, HT1376 and HTB9. Bladder cancer cells were treated for 48 h with 10 nM DHT or not, with replacement after 24 h. Expression of cell signaling proteins, was analyzed using Western Blot and RT-PCR. Subcellular localization of protein was studied using the ProteoExtract Subcellular Proteome Extraction Kit and Western blot analysis. We showed that DHT treatment significantly increased AR expression in bladder cell line HCV29. We also observed DHT-mediated activation of Akt/GSK-3β signaling pathway which plays a central role in cancer progression. Presented results also show that androgen/AR signaling is implicated in phosphorylation of eIF4E which can promote epithelial–mesenchymal transition (EMT). We indicate that AR plays an essential role in bladder cancer progression in male patients. Therefore, androgen-activated AR signaling is an attractive regulatory target for the inhibition or prevention of bladder cancer incidence in men. Springer Japan 2019-05-22 2019 /pmc/articles/PMC6570698/ /pubmed/31119584 http://dx.doi.org/10.1007/s13577-019-00255-3 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Research Article
Gil, Dorota
Zarzycka, Marta
Dulińska-Litewka, Joanna
Ciołczyk-Wierzbicka, Dorota
Lekka, Małgorzata
Laidler, Piotr
Dihydrotestosterone increases the risk of bladder cancer in men
title Dihydrotestosterone increases the risk of bladder cancer in men
title_full Dihydrotestosterone increases the risk of bladder cancer in men
title_fullStr Dihydrotestosterone increases the risk of bladder cancer in men
title_full_unstemmed Dihydrotestosterone increases the risk of bladder cancer in men
title_short Dihydrotestosterone increases the risk of bladder cancer in men
title_sort dihydrotestosterone increases the risk of bladder cancer in men
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6570698/
https://www.ncbi.nlm.nih.gov/pubmed/31119584
http://dx.doi.org/10.1007/s13577-019-00255-3
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