Abstract
A steroid hormone receptor, mineralocorticoid receptor (MR), is well known to play a critical role in maintaining normal homeostasis in the body primarily via regulating ionic and water transports. Indeed, MR antagonists have been prescribed to the patients as diuretic drugs. Meanwhile, emerging evidence has indicated that MR signaling, with or without functional interplay with glucocorticoid receptor or androgen receptor, contributes to modulating the development and progression of several types of neoplasms including genitourinary malignancies. This review summarizes the available data suggesting the involvement of MR signaling in renal cell carcinoma, prostatic adenocarcinoma, urothelial carcinoma, and other malignancies, and highlights potential underlying molecular mechanisms.
Highlights
In spite of considerable advances in diagnostic technologies as well as treatment strategies, the prognosis for patients with genitourinary malignancy, such as renal cell carcinoma, prostatic adenocarcinoma, or urothelial carcinoma, remains largely unimproved during the last few decades
While mineralocorticoid receptor (MR) antagonists, including spironolactone, have been clinically used primarily as diuretic agents, the involvement of MR signaling in the development and/or progression of neoplastic diseases remains far from being fully understood
This is supported by MR expression data indicating its down-regulation in several types of malignancies, compared with corresponding non-neoplastic tissues
Summary
In spite of considerable advances in diagnostic technologies as well as treatment strategies, the prognosis for patients with genitourinary malignancy, such as renal cell carcinoma, prostatic adenocarcinoma, or urothelial carcinoma, remains largely unimproved during the last few decades. Recent studies presumably conducted based on striking sex-specific differences in the incidence of renal cell carcinoma and urothelial carcinoma [3] have indicated an important role of AR signaling in their outgrowth [2, 4, 5] Another steroid hormone receptor, glucocorticoid receptor (GR), has been shown to function as a tumor suppressor in several types of malignancies, especially in castrationresistant prostate cancer [6, 7]. Nuclear Receptor Research mineralocorticoids and some of glucocorticoids (primarily as agonists) and other steroids, including progesterone (as an antagonist), have binding affinity for the MR [12, 13]. Aldosterone has been shown to modulate the expression of vital molecules, such as cyclooxygenase (COX)-2 [13, 22], in normal tissues
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