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

Abstract

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.

Identification of metabolism-associated genes and pathways involved in different stages of clear cell renal cell carcinoma

“…Shayman ( 7 ) revealed that eliglustat or associated analogues that inhibit glucosylceramide synthase reversed the disease phenotype and may be a potential treatment strategy for kidney disease. Recently, Czarnecka et al ( 8 ) summarized the function that hormonal signaling serves in RCC and hypothesized that inhibitors of this pathway could be used as therapeutics against this cancer. The association between circulating vitamin D and kidney cancer risk has been reported by multiple research teams ( 9 , 32 ).…”

“…For example, Linehan et al ( 6 ) considered kidney cancer a metabolic disease rather than a single disease. Shayman et al ( 7 ) and others reported that targeting glycosphingolipid metabolism, hormone signaling pathways or vitamin D metabolism may be novel therapeutic approaches for treating RCC ( 8 , 9 ). However, to the best of our knowledge, no previous study has identified the alteration of metabolism-associated genes in ccRCC.…”

Cellular effects induced by 17-β-estradiol to reduce the survival of renal cell carcinoma cells

“…In RCC, altered chemosensitivity mediated by 17-β-estradiol (E2) has been reported, so adjuvant therapy with E2 is possible as in other human diseases [ 24 , 45 ]. The molecular mechanisms of the action of E2 in RCC cells have been reported in recent years [ 8 , 10 , 13 , 43 , 45 ]. However, diverse genetic alterations are linked to renal cancer progression and to our ability to predict its risk [ 13 , 23 ].…”

Does Progesterone Influence Hela Cell Proliferation?

“…[20] Molecular data analysis also revealed the possibility of certain cancer cells proliferation induction via hormone activated pathways. [21] Progesterone also has improving effects in obese women with breast cancer. [22] It has also been suggested that progesterone is a potent hormone which inhibits the growth of human ovarian cancer cells.…”