Estriol acts as a GPR30 antagonist in estrogen receptor-negative breast cancer cells

@article{Lappano2010EstriolAA,
  title={Estriol acts as a GPR30 antagonist in estrogen receptor-negative breast cancer cells},
  author={Rosamaria Lappano and Camillo Rosano and Paola De Marco and Ernestina Marianna De Francesco and Vincenzo Pezzi and Marcello Maggiolini},
  journal={Molecular and Cellular Endocrinology},
  year={2010},
  volume={320},
  pages={162-170}
}
Estrogens are structurally related steroids that regulate important physiological processes. 17beta-estradiol (E2) is reversibly oxidized to estrone (E1) and both E2 and E1 can be irreversibly converted to estriol (E3), which also originates directly from androstenedione. The action of E2 has been traditionally explained by the binding to the estrogen receptor (ER) alpha and ER beta, however the G protein-coupled receptor (GPR) 30 has been recently involved in the rapid signaling triggered by… 
MIBE acts as antagonist ligand of both estrogen receptor α and GPER in breast cancer cells
TLDR
The exclusive antagonistic activity exerted by MIBE on ERα and GPER could represent an innovative pharmacological approach targeting breast carcinomas which express one or both receptors at the beginning and/or during tumor progression.
GPER Mediates Non-Genomic Effects of Estrogen.
TLDR
This chapter presents some of the different experimental techniques currently used to demonstrate the functional role of GPER in mediating non-genomic actions of estrogens, such as the dual luciferase assay, assessment of the involvement of GP ER in the stimulation of cell migration in breast cancer cell lines and in cancer-associated fibroblasts, and chromatin immunoprecipitation assay.
The G-protein-coupled estrogen receptor GPER in health and disease
TLDR
The physiological roles of GPER are highlighted in the reproductive, nervous, endocrine, immune and cardiovascular systems, as well as its pathological roles in a diverse array of disorders including cancer, for which GPER is emerging as a novel therapeutic target and prognostic indicator.
Unraveling the Role of GPER in Breast Cancer
TLDR
GPER may be considered as a valuable target toward novel therapeutic strategies against the development of breast cancer because the promiscuous activity exerted by antiestrogens, which act as GPER agonists and antagonists of the nuclear estrogen receptors, addresses the need of new selective estrogen receptor inhibitors.
AHR and GPER mediate the stimulatory effects induced by 3-methylcholanthrene in breast cancer cells and cancer-associated fibroblasts (CAFs)
TLDR
It is established that 3MC activates the EGFR/ERK/c-Fos transduction signaling through both AHR and GPER in SkBr3 cells and CAFs and is involved in the up-regulation of CYP1B1 and cyclin D1 as well as in the stimulation of growth responses induced by 3MC.
Interplay of estrogen receptors and GPR30 for the regulation of early membrane initiated transcriptional effects: A pharmacological approach
TLDR
E2-BSA, an impermeable estradiol analog, is used for a transcriptome analysis in four GREP1 positive breast cancer cell lines with different estrogen receptor profiles in order to evaluate GPER1 transcriptional effects, and two different clusters of transcripts could be identified.
The Role of GPER Signaling in Carcinogenesis: A Focus on Prostate Cancer
TLDR
This chapter summarizes the existent knowledge concerning the structural and molecular aspects of GPER, its known ligands and activated pathways, as well as its role over the known hallmarks of cancer: exacerbated proliferation, resistance to apoptosis, stimulated migration and invasion, induction of angiogenesis, and the metabolic reprogramming.
A calixpyrrole derivative acts as an antagonist to GPER, a G-protein coupled receptor: mechanisms and models
TLDR
Evidence is provided on the molecular mechanisms through which a calixpyrrole derivative acts as a GPER antagonist in different model systems, such as breast tumor cells and cancer-associated fibroblasts obtained from breast cancer patients.
Inhibition of GPR30 by estriol prevents growth stimulation of triple-negative breast cancer cells by 17β-estradiol
TLDR
Specific pharmacological inhibition of GPR30 might become a promising targeted therapy for TNBC in future.
Exogenous hormonal regulation in breast cancer cells by phytoestrogens and endocrine disruptors.
TLDR
Chemistry, structure and classification, estrogen signaling and the consequences of the interactions of estrogens, phytoestrogens and xenoestrogens with their receptors, the complex interactions of endogenous and exogenous ligands, the evaluation of the health risks related to xenoESTrogens, and the perspectives toward the synthesis of potent third generation selective estrogen receptor modulators (SERMs) are discussed.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 83 REFERENCES
The G Protein-Coupled Receptor GPR30 Mediates the Proliferative Effects Induced by 17β-Estradiol and Hydroxytamoxifen in Endometrial Cancer Cells
TLDR
A new mode of action of E2 and OHT in endometrial cancer cells is demonstrated, contributing to a better understanding of the molecular mechanisms involved in their uterine agonistic activity.
GPR30: a novel therapeutic target in estrogen-related disease.
TLDR
Unraveling the pharmacological profiles and specificities of ERalpha, ERbeta and GPR30 will be vital for understanding not only the physiological roles of each receptor but also for the development of the next generation of receptor-specific drugs.
17β-Estradiol, Genistein, and 4-Hydroxytamoxifen Induce the Proliferation of Thyroid Cancer Cells through the G Protein-Coupled Receptor GPR30
TLDR
The G protein-coupled receptor 30 (GPR30) and the mitogen-activated protein kinase (MAPK) pathway mediate both the up-regulation of c-fos and the growth response to E2, G, and OHT in TC cells studied, which provides new insight into the molecular mechanisms through which estrogens may induce the progression of TC.
G-Protein–Coupled Receptor 30 and Estrogen Receptor-α Are Involved in the Proliferative Effects Induced by Atrazine in Ovarian Cancer Cells
TLDR
Atrazine stimulated the proliferation of ovarian cancer cells through the GPR30–epidermal growth factor receptor transduction pathway and the involvement of ERα, indicating a novel mechanism through which atrazine may exert relevant biological effects in cancer cells.
Structure-function relationship of estrogen receptor alpha and beta: impact on human health.
TLDR
Understanding the structural basis and the molecular mechanisms by which ER transduce E2 signals in target cells will allow to create new pharmacologic therapies aimed at the treatment of a variety of human diseases affecting the cardiovascular system, the reproductive system and the skeletal system.
Structure–function relationship of estrogen receptor α and β: Impact on human health
TLDR
Understanding the structural basis and the molecular mechanisms by which ER transduce E2 signals in target cells will allow to create new pharmacologic therapies aimed at the treatment of a variety of human diseases affecting the cardiovascular system, the reproductive system, and the skeletal system.
Effects of estrone, estradiol, and estriol on hormone-responsive human breast cancer in long-term tissue culture.
TLDR
Estriol can bind to estrogen receptor and stimulate human breast cancer in tissue culture and the data do not support an antiestrogenic role for estriol inhuman breast cancer.
Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF
TLDR
It is found that the secreted factor connective tissue growth factor (CTGF) not only contributes to promote proliferation but also mediates the GPR30‐induced stimulation of cell migration, which provides a framework for understanding the physiological and pathological functions of G PR30.
In vivo Effects of a GPR30 Antagonist
TLDR
In vivo administration of G15 reveals that GPR30 contributes to both uterine and neurological responses initiated by estrogen, and the identification and characterization of a G-1 analog, G15, that binds to G PR30 with high affinity and acts as an antagonist of estrogen signaling through GPR28.
Virtual and biomolecular screening converge on a selective agonist for GPR30
TLDR
The identification of the first G PR30-specific agonist, G-1 (1), capable of activating GPR30 in a complex environment of classical and new estrogen receptors is described.
...
1
2
3
4
5
...