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Mineralocorticoid receptor signaling inhibits bladder cancer progression.
Nagata, Yujiro; Goto, Takuro; Teramoto, Yuki; Matsukawa, Takuo; Fujimoto, Naohiro; Miyamoto, Hiroshi.
Afiliación
  • Nagata Y; Department of Pathology and Laboratory Medicine, University of Rochester Medical Center Rochester, NY, USA.
  • Goto T; James P. Wilmot Cancer Institute, University of Rochester Medical Center Rochester, NY, USA.
  • Teramoto Y; Department of Urology, University of Occupational and Environmental Health School of Medicine Kitakyushu, Japan.
  • Matsukawa T; Department of Pathology and Laboratory Medicine, University of Rochester Medical Center Rochester, NY, USA.
  • Fujimoto N; James P. Wilmot Cancer Institute, University of Rochester Medical Center Rochester, NY, USA.
  • Miyamoto H; Department of Pathology and Laboratory Medicine, University of Rochester Medical Center Rochester, NY, USA.
Am J Cancer Res ; 14(2): 696-708, 2024.
Article en En | MEDLINE | ID: mdl-38455412
ABSTRACT
The biological or clinical significance of mineralocorticoid receptor (MR) in urothelial cancer remains largely unknown. The present study aimed to determine the functional role of MR in bladder cancer progression. In two of the human bladder cancer lines expressing MR, treatment with a natural MR ligand, aldosterone, significantly reduced cell proliferation and migration, which was restored by three MR antagonists clinically used, spironolactone (except colony formation of androgen receptor-positive cells cultured in the presence of androgens), eplerenone, and esaxerenone. Similarly, MR knockdown via shRNA virus infection resulted in significant increases in cell viability/migration, as well as colony formation, compared with control sublines. In addition, MR knockdown augmented the expression of ß-catenin, c-fos, and N-cadherin, and lowered that of E-cadherin and p53, indicating the induction of the cadherin switching. Immunohistochemistry in surgical specimens detected MR signals in 58 (92.1%; 36.5% weakly-positive/1+, 44.4% moderately-positive/2+, and 11.1% strongly-positive/3+) of 63 muscle-invasive bladder cancers, which was significantly lower than in adjacent non-neoplastic urothelial tissues (100%; 15.7% 1+, 37.3% 2+, and 47.1% 3+). Moreover, patients with MR-high (3+) tumor had a significantly lower risk of cancer-specific mortality (P=0.039). Multivariable analysis further showed that strong MR expression was an independent predictor of cancer-specific survival in patients with muscle-invasive bladder cancer (hazard ratio 0.117, P=0.039). These findings suggest that MR signaling functions as a tumor suppressor in urothelial carcinoma and prevents tumor growth. Accordingly, there is a possibility that the concurrent use of anti-mineralocorticoids, particularly eplerenone and esaxerenone, in patients with bladder cancer rather contributes to the promotion of disease progression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Am J Cancer Res Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Am J Cancer Res Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos