Aldosterone mediates metastatic spread of renal cancer via the G protein-coupled estrogen receptor (GPER)

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Ross D FeldmanRobert Gros

Abstract

Although aldosterone is a known regulator of renal and cardiovascular function, its role as a regulator of cancer growth and spread has not been widely considered. This study tested the hypothesis that aldosterone regulates cancer cell growth/spread via G protein-coupled estrogen receptor (GPER) activation. In vitro in murine renal cortical adenocarcinoma (RENCA) cells, a widely used murine in vitro model for the study of renal cell adenocarcinoma, aldosterone increased RENCA cell proliferation to a maximum of 125 ± 3% of control at a concentration of 10 nM, an effect blocked by the GPER antagonist G15 or by GPER knockdown using short interfering (sh) RNA techniques. Further, aldosterone increased RENCA cell migration to a maximum of 170 ± 20% of control at a concentration of 100 nM, an effect also blocked by G15 or by GPER down-regulation. In vivo, after orthotopic RENCA cell renal transplantation, pulmonary tumor spread was inhibited by pharmacologic blockade of aldosterone effects with spironolactone (percentage of lung occupied by metastasis: control = 68 ± 13, spironolactone = 26 ± 8, P < 0.05) or inhibition of aldosterone synthesis with a high dietary salt diet (percentage of lung: control = 44 ± 6, high salt = 12 ± 3, P ...Continue Reading

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Citations

Jan 28, 2017·The Journal of Steroid Biochemistry and Molecular Biology·Martin Wehling
Mar 30, 2017·The Journal of Endocrinology·Stefanie RuhsClaudia Grossmann
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Feb 1, 2020·Redox Biology·Carolyn M Klinge
Sep 18, 2018·Cancer Letters·Daoshan ZhengZhaoyu Li

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