Evidence for aldosterone-dependent growth of renal cell carcinoma.
Int J Exp Pathol
; 95(4): 244-50, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-24802662
ABSTRACT
The aim if this study was to investigate the hypothesis that K-RAS 4A is upregulated in a mineralocorticoid-dependent manner in renal cell carcinoma and that this supports the proliferation and survival of some renal cancers. Expression of the K-RAS in renal tumour tissues and cell lines was examined by real-time PCR and Western blot and mineralocorticoid receptor, and its gatekeeper enzyme 11ß-hydroxysteroid dehydrogenase-2 was examined by immunocytochemistry on a tissue microarray of 27 cases of renal cell carcinoma. Renal cancer cells lines 04A018 (RCC4 plus VHL) and 04A019 (RCC4 plus vector alone) were examined for the expression of K-RAS4A and for the effect on K-RAS expression of spironolactone blockade of the mineralocorticoid receptor. K-RAS4A was suppressed by siRNA, and the effect on cell survival, proliferation and activation of the Akt and Raf signalling pathways was investigated in vitro. K-RAS4A was expressed in RCC tissue and in the renal cancer cell lines but K-RAS was downregulated by spironolactone and upregulated by aldosterone. Spironolactone treatment and K-RAS suppression both led to a reduction in cell number in vitro. Both Akt and Raf pathways showed activation which was dependent on K-RAS expression. K-RAS expression in renal cell carcinoma is at least partially induced by aldosterone. Aldosterone supports the survival and proliferation of RCC cells by upregulation of K-RAS acting through the Akt and Raf pathways.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Renais
/
Proteínas Proto-Oncogênicas
/
Proteínas ras
/
Proliferação de Células
/
Aldosterona
/
Neoplasias Renais
Limite:
Humans
Idioma:
En
Revista:
Int J Exp Pathol
Assunto da revista:
PATOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Reino Unido