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

Czarnecka,Anna M.; Niedzwiedzka,Magdalena; Porta,Camillo; Szczylik,Cezary

doi:10.3892/ijo.2016.3460

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

Authors:
- Anna M. Czarnecka
- Magdalena Niedzwiedzka
- Camillo Porta
- Cezary Szczylik
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Affiliations: Department of Oncology, Military Institute of Medicine, Warsaw, Poland, Medical Oncology, IRCCS San Matteo University Hospital Foundation, Pavia, Italy
Published online on: March 28, 2016 https://doi.org/10.3892/ijo.2016.3460
Pages: 2221-2235

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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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