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

Wu, Sheng‐Tang; Ku, Wei-Chi; Huang, Chun-Ta; Wang, Yen-Chieh; Lin, Chih Kuang; Chen, Shaokuan

doi:10.1186/s12929-016-0282-z

Cited by 8 publications

(4 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…10 μM, for more than 6 months (16), and confirmed that SunR 786-O cells showed less growth inhibition by sunitinib than PAR cells (p<0.01) (Figure 1A). In agreement with previous studies (8,9,13), estrogen repressed growth of both PAR and SunR 786-O cells at relatively high concentrations (1 to 5 μM) (Figure 1B).…”

Section: Gper1 Agonist G-1 Inhibited Cell Growth Of Both Par Andsupporting

confidence: 93%

See 1 more Smart Citation

G-Protein-coupled Estrogen Receptor 1 Agonist G-1 Perturbs Sunitinib Resistance-related Phosphoproteomic Signatures in Renal Cell Carcinoma

Chen

Wang

Lin

et al. 2021

Cancer Genomics Proteomics

Self Cite

View full text Add to dashboard Cite

Background: Metastatic renal cell carcinoma (RCC) often develops resistance to first-line targeted therapy such as sunitinib. G-Protein-coupled estrogen receptor 1 (GPER1) agonist G-1 was recently reported to regulate RCC physiology but the role of G-1 in RCC tumorigenesis and sunitinib resistance remains largely unknown. Materials and Methods: Parental and sunitinib-resistant 786-O cells were treated with GPER1 agonist G-1, and quantitative phosphoproteomics was performed. Bioinformatic analyses and validations, including immunoblotting, cell migration, and cell cycle distribution, were performed. Results: G-1 repressed cell proliferation and migration in both parental and sunitinib-resistant 786-O cells. Phosphoproteomic signatures, including phosphoinositide 3-kinase and protein kinase B (PI3K-AKT) as well as other pathways, were upregulated in sunitinib-resistant cells but application of G-1 reversed this effect. Among phosphoprotein candidates, activating transcription factor 2 (ATF2) Thr69/71 phosphorylation was antagonistically regulated by sunitinib resistance and G-1. Conclusion: Our results open up the possibility for managing RCC and sunitinib resistance by GPER1 agonist G-1 and its regulated pathways.Renal cell carcinoma (RCC) is the leading cause of kidney malignancy, contributing to an estimated 4-5% of new cases in 2020 (1). In addition to radical or partial nephrectomy, sunitinib is the first-line standard therapy for low-risk recurrent or metastatic RCC (2, 3). Primary or secondary resistance, however, usually develops after sunitinib administration (4). Although the combination of other target therapeutics, such as immune checkpoint inhibitors, seems to be a promising treatment option (5), there is still a need to investigate alternative strategies for managing RCC, especially in cases of sunitinib resistance.The incidence of RCC has a male-to-female ratio of 2:1 in young patients but becomes approximately 1:1 in patients over 70 years old (6), implying the inhibitory role of estrogen in RCC carcinogenesis. Estrogen can repress RCC growth by non-genomic signaling pathways via classical, nuclear estrogen receptors (7-9). In addition to nuclear estrogen receptors, G-protein-coupled estrogen receptor 1 (GPER1) was identified as a non-classical estrogen receptor, and its expression correlated with tumorigenesis and poor prognosis in several cancer types, including breast and prostate cancer (10). Treatment of in vitro cancer cell lines by the GPER1 agonist, G-1, led to variable results. For example, G-1 inhibited cell growth in prostate cancer (11) but promoted cell survival and migration in RCC cell lines (12). Recently, we demonstrated that estrogen inhibited RCC cell growth and alleviated sunitinib resistance in vitro through estrogen-triggered modulation of phosphorylation (9, 13). However, it remains unclear whether G-1 regulates phosphorylation dynamics in RCC tumorigenesis as well as and sunitinib resistance.Quantitative phosphoproteomics has been used to study phosphorylation signaling in ca...

show abstract

Section: Gper1 Agonist G-1 Inhibited Cell Growth Of Both Par Andsupporting

confidence: 93%

“…It has been shown that estrogen represses RCC cell growth via classical estrogen receptors (8,9), and perturbs sunitinib resistance in in vitro RCC cell culture (13). The role of nonclassical estrogen receptor GPER1 in RCC physiology, however, is still unclear.…”

Section: Discussionmentioning

confidence: 99%

G-Protein-coupled Estrogen Receptor 1 Agonist G-1 Perturbs Sunitinib Resistance-related Phosphoproteomic Signatures in Renal Cell Carcinoma

Chen

Wang

Lin

et al. 2021

Cancer Genomics Proteomics

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the past few decades, sex hormones have been shown to have a certain effect on the development and progression of RCC 26 , 27 . However, the effect of sex hormone in Xp11.2 tRCCs was not evaluated.…”

Section: Discussionmentioning

confidence: 99%

Estrogen associates with female predominance in Xp11.2 translocation renal cell carcinoma

Zhu

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Based on the epidemiological characteristics of susceptibility and age selectivity for women in Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC), we inferred that estrogen was to be blamed. Rad54 like 2 (Rad54l2) which might be one of key effector proteins of DNA damage mediated by estrogen was downregulated in numerous cancers, however, its role in epidemiological characteristics of Xp11.2 tRCC was needed to further study. We reviewed 1005 Xp11.2 tRCC cases and collected estrogen data and then compared the onset time of Xp11.2 tRCC cases in female with estrogen changing trend. An RNA-sequencing was performed in estrogen treated HK-2 cells and subsequently bioinformatic analysis was applied based on the Cancer Genome Atlas (TCGA) and GEO database. The male-to-female ratio of Xp11.2 tRCC was 1:1.4 and the median age of onset was 29.7 years old. The onset trend of female was similar to estrogen physiological rhythm (r = 0.67, p < 0.01). In Xp11.2 tRCC and HK-2 cells after estrogen treatment, Rad54l2 was downregulated, and GSEA showed that pathways significantly enriched in DNA damage repair and cancer related clusters after estrogen treated, as well as GO and KEGG analysis. Downregulation of Rad54l2 was in numerous cancers, including renal cell carcinoma (RCC), in which Rad54l2 expression was significantly decreased in male, age over 60 years old, T2&T3&T4 stages, pathologic SII&SIII&SIV stages as well as histologic G3&G4 grades, and cox regression analysis proved that Rad54l2 expression was a risk factor for overall survival, disease-specific survival and progression-free interval in univariate analysis. There existed female predominance in Xp11.2 tRCC and Rad54l2 might play vital role in estrogen mediating female predominance in Xp11.2 tRCC.

show abstract

“…In RCC, the level and frequency of ER expression is highly variable, with a higher frequency of ERβ than ERα, and there are very limited and contrasting data concerning the role of estrogenic signals in the tumorigenesis and development of RCC [52,[70][71][72][73]. Previous studies demonstrated that estrogen, through ERβ signaling, suppressed the proliferation, migration and invasion of RCC cells and increased RCC apoptosis [74][75][76]. Analysis of the molecular mechanisms revealed that estrogen reduced the expression of downstream genes, such as AKT, extracellular signal-regulated kinase (ERK) and Janus kinase (JAK) signaling pathways and increased the apoptotic genes (BH3 interactingdomain death agonist (Bid), Caspase-3, Caspase-8 and Caspase-9), through ERβ activation, suggesting that this receptor could have an inhibitory effect in RCC [75,76].…”

Section: The Estrogen Signalling Axismentioning

confidence: 99%

Sex and Gender Differences in Kidney Cancer: Clinical and Experimental Evidence

Peired

Campi

Angelotti

et al. 2021

Cancers

View full text Add to dashboard Cite

Sex and gender disparities have been reported for different types of non-reproductive cancers. Males are two times more likely to develop kidney cancer than females and have a higher death rate. These differences can be explained by looking at genetics and genomics, as well as other risk factors such as hypertension and obesity, lifestyle, and female sex hormones. Examination of the hormonal signaling pathways bring further insights into sex-related differences. Sex and gender-based disparities can be observed at the diagnostic, histological and treatment levels, leading to significant outcome difference. This review summarizes the current knowledge about sex and gender-related differences in the clinical presentation of patients with kidney cancer and the possible biological mechanisms that could explain these observations. Underlying sex-based differences may contribute to the development of sex-specific prognostic and diagnostic tools and the improvement of personalized therapies.

show abstract

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

Cited by 8 publications

References 48 publications

G-Protein-coupled Estrogen Receptor 1 Agonist G-1 Perturbs Sunitinib Resistance-related Phosphoproteomic Signatures in Renal Cell Carcinoma

G-Protein-coupled Estrogen Receptor 1 Agonist G-1 Perturbs Sunitinib Resistance-related Phosphoproteomic Signatures in Renal Cell Carcinoma

Estrogen associates with female predominance in Xp11.2 translocation renal cell carcinoma

Sex and Gender Differences in Kidney Cancer: Clinical and Experimental Evidence

Contact Info

Product

Resources

About