scholarly journals The G-protein-coupled estrogen receptor agonist G-1 suppresses proliferation of ovarian cancer cells by blocking tubulin polymerization

2013 ◽  
Vol 4 (10) ◽  
pp. e869-e869 ◽  
Author(s):  
C Wang ◽  
X Lv ◽  
C He ◽  
G Hua ◽  
M-Y Tsai ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
G Protein ◽  
Receptor Agonist ◽  
Ovarian Cancer Cells ◽  
Tubulin Polymerization ◽  
G Protein Coupled

scholarly journals The G-Protein-Coupled Estrogen Receptor (GPER) Regulates Trimethylation of Histone H3 at Lysine 4 and Represses Migration and Proliferation of Ovarian Cancer Cells In Vitro

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 619
Author(s):  
Nan Han ◽  
Sabine Heublein ◽  
Udo Jeschke ◽  
Christina Kuhn ◽  
Anna Hester ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Estrogen Receptor ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Patients ◽  
G Protein ◽  
Histone H3 ◽  
Ovarian Cancer Cells ◽  
G Protein Coupled

Histone H3 lysine 4 trimethylation (H3K4me3) is one of the most recognized epigenetic regulators of transcriptional activity representing, an epigenetic modification of Histone H3. Previous reports have suggested that the broad H3K4me3 domain can be considered as an epigenetic signature for tumor-suppressor genes in human cells. G-protein-coupled estrogen receptor (GPER), a new membrane-bound estrogen receptor, acts as an inhibitor on cell growth via epigenetic regulation in breast and ovarian cancer cells. This study was conducted to evaluate the relationship of GPER and H3K4me3 in ovarian cancer tissue samples as well as in two different cell lines (Caov3 and Caov4). Silencing of GPER by a specific siRNA and two selective regulators with agonistic (G1) and antagonistic (G15) activity were applied for consecutive in vitro studies to investigate their impacts on tumor cell growth and the changes in phosphorylated ERK1/2 (p-ERK1/2) and H3K4me3. We found a positive correlation between GPER and H3K4me3 expression in ovarian cancer patients. Patients overexpressing GPER as well as H3K4me3 had significantly improved overall survival. Increased H3K4me3 and p-ERK1/2 levels and attenuated cell proliferation and migration were observed in Caov3 and Caov4 cells via activation of GPER by G1. Conversely, antagonizing GPER activity by G15 resulted in opposite effects in the Caov4 cell line. In conclusion, interaction of GPER and H3K4me3 appears to be of prognostic significance for ovarian cancer patients. The results of the in vitro analyses confirm the biological rationale for their interplay and identify GPER agonists, such as G1, as a potential therapeutic approach for future investigations.

Estradiol Attenuates EGF-Induced Rapid uPAR Mobilization and Cell Migration via the G-protein-Coupled Receptor 30 in Ovarian Cancer Cells

2009 ◽  
Vol 19 (2) ◽  
pp. 214-222 ◽  
Author(s):  
Emir Henic ◽  
Vera Noskova ◽  
Gunilla Høyer-Hansen ◽  
Stefan Hansson ◽  
Bertil Casslén
Keyword(s):  
Ovarian Cancer ◽  
Cell Migration ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cancer Cells ◽  
G Protein ◽  
Ovarian Cancer Cells ◽  
Upar Expression ◽  
Epidermal Growth ◽  
G Protein Coupled

Epidermal growth factor (EGF) stimulates proliferation and migration in ovarian cancer cells, and high tumor expression of the EGF system correlates with poor prognosis. Epidermal growth factor upregulates urokinase plasminogen activator receptor (uPAR) on the cell surface via 3 distinct mechanisms: rapid mobilization of uPAR from detergent-resistant domains, increased mRNA, and decreased degradation. G-protein-coupled receptor 30 (GPR30) is a newly identified membrane estrogen receptor (ER).The objective of this study was to explore the effects of 17β-estradiol (E2) on uPAR expression and cell migration in ovarian cancer cells and further to identify the ER involved.We used 7 ovarian cancer cell lines, cell migration assay, cellular binding of 125I-uPA, cellular degradation of 125I-uPA/PAI-1 complex, enzyme-linked immunosorbent assay for uPAR, solid-phase enzyme immunoassay for ERα, and quantitative polymerase chain reaction.Estradiol attenuates the stimulatory effect of EGF on cell migration and uPAR expression. Specifically, E2 reduces the very rapid increase of detergent extractable uPAR, which occurs within minutes of EGF stimulation and probably represents mobilization of uPAR from detergent-resistant domains such as lipid rafts. Estradiol influenced neither the amount of uPAR mRNA nor the rate of uPAR degradation or solubilization. The nuclear ER antagonists ICI 182780 and tamoxifen, which are GPR30 agonists, as well as the specifically constructed GPR30 agonist G1, mimicked the effect of E2 on uPAR expression and cell migration. OVCAR-3 cells express mRNA for GPR30.Estradiol attenuates EGF-induced mobilization of ligated uPAR from detergent-resistant domains and subsequent migration in ovarian cancer cells. The response to various ER ligands indicates that this effect is mediated via the membrane ER GPR30.

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