Androgen receptor inducing bladder cancer progression by promoting an epithelial-mesenchymal transition
W Jitao1, H Jinchen, L Qingzuo
1Department of Urology, Yantai Yuhuangding Hospital, Yantai, Shandong province, China.
Abstract:
The study investigated the role of androgen receptor (AR) as a potential target for the treatment of bladder cancer in regulating epithelial-mesenchymal transition or transformation (EMT). Cell proliferation, and migration capacity were determined in bladder cancer T24 cells treated with small interfering RNA directed against AR, and expression levels of E-cadherin, β-catenin and N- cadherin were assessed using quantitative reverse transcription PCR (qRT-PCR). Tumour cell growth was evaluated in vivo in T24 tumour-bearing nude mice receiving electroporation-assisted administration of anti-AR small interfering RNA. It was found that low AR expression decreased proliferation and migration of bladder cancer cells. In vivo experiments showed that silencing AR expression significantly suppressed AR-positive bladder tumour growth with decreased cell proliferation. Low AR level of T24 bladder cancer cells treated with dehydrotestosterone (DHT) decreased expression of E-cadherin, β-catenin and N-cadherin expression, indicating a strong sensitivity to the EMT and In cells with low AR content, TGF-β induced down-regulation of E-cadherin and β-catenin. It is concluded that suppression of AR expression decreased the production of TGF-β, inhibiting EMT and bladder cancer cell growth in vitro and in vivo, implying that its use might be a potential therapeutic target for the treatment of bladder cancer.
Insights
Suppressing androgen receptor (AR) inhibits bladder cancer growth and epithelial-mesenchymal transition (EMT). Silencing AR reduces tumor proliferation and migration, suggesting AR as a potential therapeutic target for bladder cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Androgen receptor (AR) plays a role in various cancers.
- Epithelial-mesenchymal transition (EMT) is crucial for cancer progression and metastasis.
- The specific role of AR in bladder cancer EMT requires further elucidation.
Purpose of the Study:
- To investigate the role of androgen receptor (AR) in regulating epithelial-mesenchymal transition (EMT) in bladder cancer.
- To evaluate the therapeutic potential of targeting AR for bladder cancer treatment.
Main Methods:
- Utilized T24 bladder cancer cells treated with small interfering RNA (siRNA) against AR.
- Assessed cell proliferation, migration, and expression of EMT markers (E-cadherin, β-catenin, N-cadherin) via qRT-PCR.
- Evaluated tumor growth in vivo using T24 tumor-bearing nude mice with electroporation-assisted anti-AR siRNA administration.
Main Results:
- Silencing AR expression significantly decreased bladder cancer cell proliferation and migration in vitro.
- In vivo studies demonstrated that suppressed AR expression inhibited AR-positive bladder tumor growth.
- Reduced AR levels decreased E-cadherin, β-catenin, and N-cadherin expression, indicating inhibition of EMT.
- Suppression of AR expression led to decreased TGF-β production, further inhibiting EMT and tumor growth.
Conclusions:
- AR plays a significant role in promoting bladder cancer cell proliferation, migration, and EMT.
- Suppression of AR expression effectively inhibits bladder cancer growth both in vitro and in vivo.
- Targeting AR represents a promising therapeutic strategy for bladder cancer treatment.
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