Evidence for aldosterone-dependent growth of renal cell carcinoma
| Autor: | Sharon King, Sarah Galbraith, Lesley Christie, Stewart Fleming, Susan E. Bray |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Cell Survival Biology In Vitro Techniques Spironolactone urologic and male genital diseases Pathology and Forensic Medicine Proto-Oncogene Proteins p21(ras) chemistry.chemical_compound Mineralocorticoid receptor Downregulation and upregulation Renal cell carcinoma Internal medicine Cell Line Tumor Proto-Oncogene Proteins medicine Biomarkers Tumor Humans Molecular Biology Protein kinase B Aldosterone Carcinoma Renal Cell Cell Proliferation Cell Biology Original Articles medicine.disease Kidney Neoplasms Endocrinology Receptors Mineralocorticoid chemistry Cell culture Tissue Array Analysis Cancer cell ras Proteins 11-beta-Hydroxysteroid Dehydrogenases raf Kinases Proto-Oncogene Proteins c-akt Signal Transduction |
| Popis: | 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 11β-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. |
| Databáze: | OpenAIRE |
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