Evidence for aldosterone-dependent growth of renal cell carcinoma

Sharon King, Susan Bray, Sarah Galbraith, Lesley Christie, Stewart Fleming (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    12 Citations (Scopus)

    Abstract

    The aim of 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.

    Original languageEnglish
    Pages (from-to)244-250
    Number of pages7
    JournalInternational Journal of Experimental Pathology
    Volume95
    Issue number4
    Early online date7 May 2014
    DOIs
    Publication statusPublished - Aug 2014

    Fingerprint

    Spironolactone
    Kidney Neoplasms
    Aldosterone
    Renal Cell Carcinoma
    Mineralocorticoid Receptors
    Growth
    Cell Proliferation
    11-beta-Hydroxysteroid Dehydrogenases
    Cell Line
    Mineralocorticoids
    Tumor Cell Line
    Small Interfering RNA
    Real-Time Polymerase Chain Reaction
    Cell Survival
    Up-Regulation
    Down-Regulation
    Cell Count
    Western Blotting
    Immunohistochemistry
    Kidney

    Cite this

    King, Sharon ; Bray, Susan ; Galbraith, Sarah ; Christie, Lesley ; Fleming, Stewart. / Evidence for aldosterone-dependent growth of renal cell carcinoma. In: International Journal of Experimental Pathology. 2014 ; Vol. 95, No. 4. pp. 244-250.
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    abstract = "The aim of 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 11{\ss}-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.",
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    Evidence for aldosterone-dependent growth of renal cell carcinoma. / King, Sharon; Bray, Susan; Galbraith, Sarah; Christie, Lesley; Fleming, Stewart (Lead / Corresponding author).

    In: International Journal of Experimental Pathology, Vol. 95, No. 4, 08.2014, p. 244-250.

    Research output: Contribution to journalArticle

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    AU - King, Sharon

    AU - Bray, Susan

    AU - Galbraith, Sarah

    AU - Christie, Lesley

    AU - Fleming, Stewart

    N1 - © 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology.

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    N2 - The aim of 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.

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