title: Androgen receptor inducing bladder cancer progression by promoting an epithelial-mesenchymal transition.
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.
authors: Department of Urology, Yantai Yuhuangding Hospital, Yantai, Shandong province, China.
authors: W
authors: W
authors: Jitao
authors: H
authors: H
authors: Jinchen
authors: L
authors: L
authors: Qingzuo
authors: C
authors: C
authors: Li
authors: S
authors: S
authors: Lei
authors: W
authors: W
authors: Jianming
authors: G
authors: G
authors: Zhenli
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D034622:RNA Interference; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D015820:Cadherins; D011944:Receptors, Androgen; D016212:Transforming Growth Factor beta
keywords: Androgen receptor; bladder cancer; epithelial; mesenchymal transition