scholarly journals The G Protein-Coupled Receptor GPR30 Inhibits Human Urothelial Cell Proliferation

Endocrinology ◽  
2008 ◽  
Vol 149 (8) ◽  
pp. 4024-4034 ◽  
Author(s):  
Jian Teng ◽  
Zun-Yi Wang ◽  
Eric R. Prossnitz ◽  
Dale E. Bjorling
Keyword(s):  
Cell Proliferation ◽  
Cyclin D1 ◽  
G Protein ◽  
Small Interfering Rna ◽  
Urothelial Cell ◽  
Urothelial Cells ◽  
G Protein Coupled Receptor ◽  
17Β Estradiol ◽  
Interfering Rna ◽  
G Protein Coupled

We have previously shown that estrogen stimulates cell proliferation in both normal and transformed urothelial cells mainly through activation of the two primary estrogen receptors (ERs), ERα and ERβ. A growing body of evidence suggests that estrogen also initiates nongenomic effects that cannot be explained by activation of primary ERs. In the present study, we observed that urothelial cells express high amounts of GPR30, a G protein-coupled receptor recently identified as a candidate for membrane-associated estrogen binding. Membrane- impermeable bovine serum albumin-conjugated 17β-estradiol and the specific GPR30 agonist G-1 both inhibited urothelial cell proliferation in a concentration-dependent manner. Transient overexpression of GPR30 inhibited 17β-estradiol (E2)-induced cell proliferation. Decreased GPR30 expression caused by specific small interfering RNA increased E2-induced cell proliferation. These results indicate that membrane-associated inhibitory effects of E2 on cell proliferation correlate with abundance of GPR30. Although E2 induced a significant increase in caspase-3/7 activity, G-1 did not, suggesting that the GPR30-mediated inhibitory effect on cell proliferation was not caused by apoptosis. Furthermore, we found that G-1 failed to induce c-fos, c-jun, and cyclin D1 expression, and GPR30 overexpression abolished E2-induced c-fos, c-jun, and cyclin D1 expression. However, inactivation of GPR30 by small interfering RNA increased c-fos, c-jun, and cyclin D1 expression. These results suggest that GPR30-mediated inhibition of urothelial cell proliferation is the result of decreased cyclin D1 by down-regulation of activation protein-1 signaling.

scholarly journals Small interfering RNA-mediated silencing of G-protein-coupled receptor 137 inhibits growth of osteosarcoma cells

2018 ◽  
Vol 11 ◽  
pp. 17-22 ◽  
Author(s):  
Hao Li ◽  
Xiaodong Fu ◽  
Yingjian Gao ◽  
Xiaomiao Li ◽  
Yi Shen ◽  
...  
Keyword(s):  
G Protein ◽  
Small Interfering Rna ◽  
Osteosarcoma Cells ◽  
G Protein Coupled Receptor ◽  
Interfering Rna ◽  
G Protein Coupled

scholarly journals The Novel Estrogen Receptor, G Protein-Coupled Receptor 30, Mediates the Proliferative Effects Induced by 17β-Estradiol on Mouse Spermatogonial GC-1 Cell Line

Endocrinology ◽  
2008 ◽  
Vol 149 (10) ◽  
pp. 5043-5051 ◽  
Author(s):  
Rosa Sirianni ◽  
Adele Chimento ◽  
Carmen Ruggiero ◽  
Arianna De Luca ◽  
Rosamaria Lappano ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathways ◽  
Cell Line ◽  
G Protein ◽  
Knockout Mice ◽  
Growth Factor Receptor ◽  
Estrogen Signaling ◽  
G Protein Coupled Receptor ◽  
17Β Estradiol ◽  
G Protein Coupled

Many studies have indicated that estrogens could have a role in the regulation of testicular function. However, it remains uncertain whether estrogens are able to directly activate signaling pathways in male germ cells. Estrogens are synthesized by the enzyme aromatase and classically act by binding to estrogen receptors (ERs)-α and ERβ. Knockout mice for both receptor isoforms exhibit a testicular phenotype that is less severe than aromatase knockout mice, suggesting the existence of an estrogen-binding receptor that may compensate for the lack of ERs. Recently studies using estrogen-sensitive tumor cell lines have demonstrated that the G-protein-coupled receptor (GPR)-30 binds and mediates estrogen action through the activation of the epidermal growth factor receptor (EGFR)/ERK/fos transduction pathway. The present study investigated the ability of 17β-estradiol (E2) to activate this pathway in the mouse spermatogonial cell line (GC-1). Using the GC-1 cell line as a model system, we demonstrated that GC-1 cells express GPR30 and ERα but not ERβ. E2, the selective GPR30 agonist G1, and the selective ERα agonist 4,4′,4″-(4-propyl-[1H]pyrazole-1,3,5-triyl) trisphenol activated the rapid ERK1/2-fos signaling cascade. This response was abrogated by the EGFR inhibitor AG1478, ERK inhibitor PD98059 and ER inhibitor ICI 182780, or by silencing GPR30 expression. Moreover, E2 and G1 up-regulated cyclin D1 expression and GC-1 cell proliferation. Our results indicate for the first time that estrogens, through a cross talk between GPR30 and ERα, activate the rapid EGFR/ERK/fos pathway, which in turn stimulate mouse GC-1 cell proliferation. Further studies to elucidate the involvement of rapid estrogen signaling pathways in the regulation of male fertility are warranted.

Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation

Nature ◽  
1997 ◽  
Vol 385 (6614) ◽  
pp. 347-350 ◽  
Author(s):  
Leandros Arvanitakis ◽  
Elizabeth Geras-Raaka ◽  
Anjali Varma ◽  
Marvin C. Gershengorn ◽  
Ethel Cesarman
Keyword(s):  
Cell Proliferation ◽  
G Protein ◽  
Human Herpesvirus ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled ◽  
Constitutively Active

scholarly journals Leucine-rich repeat-containing G-protein-coupled receptor 8 in mature glomeruli of developing and adult rat kidney and inhibition by insulin-like peptide-3 of glomerular cell proliferation

2006 ◽  
Vol 189 (2) ◽  
pp. 397-408 ◽  
Author(s):  
P Fu ◽  
P-J Shen ◽  
C-X Zhao ◽  
D J Scott ◽  
C S Samuel ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
G Protein ◽  
Binding Sites ◽  
Renal Cortex ◽  
Mesangial Cells ◽  
Rat Kidney ◽  
Leucine Rich Repeat ◽  
G Protein Coupled Receptor ◽  
Adult Rat ◽  
G Protein Coupled

Leucine-rich repeat-containing G-protein-coupled receptor 8 (LGR8, or RXFP2) is a member of the type C leucine-rich repeat-containing G protein-coupled receptor family, and its endogenous ligand is insulin-like peptide-3 (INSL3). Although LGR8 expression has been demonstrated in various human tissues, including testis, ovary, brain and kidney, the precise roles of this receptor in many of these tissues are unknown. In an effort to better understand INSL3–LGR8 systems in the rat, we cloned the full-length Lgr8 cDNA and investigated the presence and cellular localization of Lgr8 mRNA expression in adult and developing rat kidney. On the basis of these findings, we investigated the presence and distribution of renal 125I-labelled human INSL3-binding sites and the nature of INSL3–LGR8 signalling in cultured renal cells. Thus, using in situ hybridization histochemistry, cells expressing Lgr8 mRNA were observed in glomeruli of renal cortex from adult rats and were tentatively identified as mesangial cells. Quantitative, real-time PCR analysis of the developmental profile of Lgr8 mRNA expression in kidney revealed highest relative levels at late stage gestation (embryonic day 18), with a sharp decrease after birth and lowest levels in the adult. During development, silver grains associated with Lgr8 mRNA hybridization were observed overlying putative mesangial cells in mature glomeruli, with little or no signal associated with less-mature glomeruli. In adult and developing kidney, specific 125I-INSL3-binding sites were associated with glomeruli throughout the renal cortex. In primary cultures of glomerular cells, synthetic human INSL3 specifically and dose-dependently inhibited cell proliferation over a 48 h period, further suggesting the presence of functional LGR8 (receptors) on these cells (mesangial and others). These findings suggest INSL3–LGR8 signalling may be involved in the genesis and/or developmental maturation of renal glomeruli and possibly in regulating mesangial cell density in adult rat kidney.

The G Protein–Coupled Receptor GPR30 Mediates the Nontranscriptional Effect of Estrogen on the Activation of PI3K/Akt Pathway in Endometrial Cancer Cells

2013 ◽  
Vol 23 (1) ◽  
pp. 52-59 ◽  
Author(s):  
Xin Ge ◽  
Ruixia Guo ◽  
Yuhuan Qiao ◽  
Yancai Zhang ◽  
Jia Lei ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endometrial Cancer ◽  
Cancer Cells ◽  
G Protein ◽  
Akt Pathway ◽  
G Protein Coupled Receptor ◽  
Down Regulation ◽  
Phosphorylated Akt ◽  
Ishikawa Cells ◽  
G Protein Coupled

ObjectiveThe goal of this study was to investigate the effect of G protein–coupled receptor 30 (GPR30) on the activation of PI3K/Akt pathway induced by E2 in endometrial cancer cells.Methods and materialsImmunohistochemistry was performed to determine the location and expression of GPR30, estrogen receptors (ERs), Akt, and phosphorylated Akt. We also investigated the expression of GPR30, ERs, and the level of phosphorylation of Akt induced by E2 in endometrial cancer cells, Ishikawa cells, and HEC-1A cells. We down-regulated the expression of GPR30 in endometrial cancer cell lines by transfection with shGPR30-pGFP-V-RS, a GPR30 antisense expression vector. The cells were then subjected to a proliferation assay. Immunoprecipitation assay was performed to determine whether GPR30 directly bind to PI3K. The stable transfected cells resuspension of 100 μL (5 × 106 cells) was injected subcutaneously into the right flank of athymic mice to perform xenograft tumor formation assays.ResultsE2 stimulated cell proliferation and induced GPR30 expression and PI3K/Akt pathway activation in endometrial cancer cells, Ishikawa cells, and HEC-1A cells, whereas the expression of ERs remained unchangeable. Down-regulation of GPR30 decreased the phosphorylation of Akt and reduced cell proliferation, and GPR30 did not bind to PI3K. Down-regulation of GPR30 significantly inhibited the tumor growth of HEC-1A cells in athymic nude mice.ConclusionsThese findings suggest that GPR30 mediates the nontranscriptional effect of estrogen on the activation of PI3K/Akt pathway in endometrial cancer cells.

Sign in / Sign up

Export Citation Format

Share Document