Steroid Receptors in Renal Cell Carcinoma

Yakirevich, Evgeny; Matoso, Andrés; Morris, David J.; Resnick, Murray B.

doi:10.5772/26993

Cited by 3 publications

(4 citation statements)

References 139 publications

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“…Renal cell carcinoma (RCC) is hormone-dependent: AR was found in 15% of patients with RCC and inversely correlated with the histopathological stage (27% of cells were AR-positive in pT1 tumors, only 4% cells were AR-positive in pT3 tumors) and inversely correlated with the nuclear grade of receptor expression. Univariate analysis showed longer disease survival in patients with AR-positive tumors compared to patients with AR-negative tumors [57]. In our experiment, we observed a decreased level of expression of AR in the cortical region (RC, PCT, and DCT) of the kidney in the finasteride-treated rats that could be related to altered serum androgens (T and DHT) levels.…”

Section: Discussionmentioning

confidence: 47%

“…Thus, the physiology of kidney is mediated by androgen receptors (AR) localized in the cells of most parts of the nephron. In the cortex of the kidney, AR is located in various structures, predominantly in proximal and distal convoluted tubules (PCT and DCT) and shows focal expression in the parietal layer of Bowman’s capsule [53,54,55,56,57].…”

Section: Discussionmentioning

confidence: 99%

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Finasteride-Induced Inhibition of 5α-Reductase Type 2 Could Lead to Kidney Damage—Animal, Experimental Study

Baig

Kolasa

Pilutin

et al. 2019

IJERPH

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In the pharmacological treatment of prostate cancer, benign prostatic hyperplasia and androgenetic alopecia finasteride is commonly used. This drug inhibits 5α-reductase type 2, which is why finasteride affects androgen homeostasis, since testosterone (T) cannot be reduced to dihydrotestosterone (DHT). As studies on sex-related renal injuries suggest a high probability of androgen-induced renal dysfunction, the aim of this study was to determine the potential harmful effects of finasteride on the kidneys of rats. The study was performed on sexually mature male Wistar rats given finasteride. Histological sections of the kidneys were used for immunohistochemical visualization of the androgen receptor (AR), junctional proteins (occluding (Occ); E-cad, N-cad, E-/N-cadherin; β-cat, β-catenin; connexin 43 (Cx43)), proliferating cell nuclear antigen (PCNA), IL-6, and lymphocyte markers (CD3 for T cell, CD19 for B cell). The TUNEL method was used for cell apoptosis identification, and picro sirius red staining was used to assess collagen fibers thickness. The levels of T, DHT and estradiol (E2) were determined in blood serum. It was shown that finasteride treatment affected steroid hormone homeostasis, altered the expression of AR and intracellular junction proteins, changed the ratio between cell apoptosis and proliferation, and caused lymphocyte infiltration and an increase of IL-6. The thickening of collagen fibers was observed as tubular fibrosis and glomerulosclerosis. Summarizing, finasteride-induced hormonal imbalance impaired the morphology (i.e., dysplastic glomeruli, swollen proximal convoluted tubules) and physiology (changed level of detected proteins/markers expression) of the kidneys. Therefore, it is suggested that patients with renal dysfunction or following renal transplantation, with androgen or antiandrogen supplementation, should be under special control and covered by extended diagnostics, because the adverse negative effect of DHT deficiency on the progression of kidney disease cannot be ignored.

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Section: Discussionmentioning

confidence: 47%

Section: Discussionmentioning

confidence: 99%

Finasteride-Induced Inhibition of 5α-Reductase Type 2 Could Lead to Kidney Damage—Animal, Experimental Study

Baig

Kolasa

Pilutin

et al. 2019

IJERPH

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“…They act as ligand-dependent transcription factors, but there is growing evidence that these receptors can also induce gene expression through ligand-independent pathways (11). All have some recorded role in normal kidney growth and RCC development (12), although often the differential expression in RCC appears to be functionally-insignificant, because modulation of the receptors produces little therapy benefit to stop growth of RCC. In this mini review, we will concentrate on AR, ER, and the retinoid receptors.…”

Section: Steroid Hormones and Rccmentioning

confidence: 99%

“…Examples include hematologic malignancies, and autoimmunity diseases more commonly found in women. However, early studies on the linkage between AR expression and RCC progression have produced controversial findings (12). The early studies often did not differentiate AR expression in different RCC subtypes, and AR function was often disregarded.…”

Section: Androgen Receptor In Rccmentioning

confidence: 99%

Evaluation of steroid hormones and their receptors in development and progression of renal cell carcinoma

Bennett

Rajandram

et al. 2014

jkcvhl

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Steroid hormones and their receptors have important roles in normal kidney biology, and alterations in their expression and function help explain the differences in development of kidney diseases, such as nephrotic syndrome and chronic kidney disease. The distinct gender difference in incidence of renal cell carcinoma (RCC), with males having almost twice the incidence as females globally, also suggests a role for sex hormones or their receptors in RCC development and progression. There was a peak in interest in evaluating the roles of androgen and estrogen receptors in RCC pathogenesis in the late 20th century, with some positive outcomes for RCC therapy that targeted estrogen receptors, especially for metastatic disease. Since that time, however, there have been few studies that look at use of steroid hormone modulators for RCC, especially in the light of new therapies such as the tyrosine kinase inhibitors and new immune therapies, which are having some success for treatment of metastatic RCC. This review summarises past and current literature and attempts to stimulate renewed interest in research into the steroid hormones and their receptors, which might be used to effect, for example, in combination with the other newer targeted therapies for RCC.

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Hormone signaling pathways as treatment targets in renal cell cancer (Review)

Czarnecka

Niedzwiedzka

Porta

et al. 2016

International Journal of Oncology

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Abstract. Epidemiological, clinical, biochemical and genetic research has revealed that renal cell cancer (RCC) etiology is hormone-related. It was shown that hormone receptors are abnormally expressed in RCC cells. Abnormal endocrine stimulation also plays a significant role in RCC pathophysiology. Cellular proliferation, migration, angiogenesis, and drug resistance in RCC is modulated by para-and autocrine hormonal stimulation. In particular, RCC overexpression of gonadotropin-releasing hormone and its receptor was reported. On the contrary, corticotropin releasing hormone was reported to inhibit RCC cell proliferation and regulate angiogenesis. Overexpression of luteinizing hormone also promotes RCC tumor angiogenesis. Estrogen receptor α overexpression increases the transcriptional factor activity of hypoxia inducible factor HIF-1α, but estrogen receptor β has a cancer suppressive role. Glucocorticoid receptors and androgen receptor are markers of indolent RCC and assigned tumor suppressive activity. Proopiomelanocortin is upregulated in VHL-mutated renal cell carcinoma via Nur77 transcription factor signaling. In RCC, follicle-stimulating hormone receptor promotes angiogenesis and metastatic formation via VEGF release. Mineralocorticoid receptor overexpression promotes cell survival and increases RCC cell proliferation. Vitamin D receptor expression is downregulated or absent in RCC and differentiate subtypes of renal cell tumors. RAR-β promotes tumorigenesis but retinoic acid receptor γ expression correlates negatively with the TNM stage at diagnosis. Finally, progesterone receptor expression is negatively correlated with the cancer stage. Molecular data analysis revealed the possibility of renal cancer cell proliferation induction via hormone activated pathways. Inhibition of hormonal signaling may thus play a putative role in supportive therapies against this cancer type.

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Steroid Receptors in Renal Cell Carcinoma

Cited by 3 publications

References 139 publications

Finasteride-Induced Inhibition of 5α-Reductase Type 2 Could Lead to Kidney Damage—Animal, Experimental Study

Finasteride-Induced Inhibition of 5α-Reductase Type 2 Could Lead to Kidney Damage—Animal, Experimental Study

Evaluation of steroid hormones and their receptors in development and progression of renal cell carcinoma

Hormone signaling pathways as treatment targets in renal cell cancer (Review)

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