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

Rosamaria Lappano; Camillo Rosano; Paola De Marco; Ernestina Marianna De Francesco; Vincenzo Pezzi; Marcello Maggiolini

doi:10.1016/j.mce.2010.02.006

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

Mol Cell Endocrinol. 2010 May 14;320(1-2):162-70. doi: 10.1016/j.mce.2010.02.006. Epub 2010 Feb 6.

Authors

Rosamaria Lappano¹, Camillo Rosano, Paola De Marco, Ernestina Marianna De Francesco, Vincenzo Pezzi, Marcello Maggiolini

Affiliation

¹ Dipartimento Farmaco-Biologico, Università della Calabria, Rende (CS), Italy.

PMID: 20138962
DOI: 10.1016/j.mce.2010.02.006

Abstract

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 estrogens. Although the role of E2 in the development of breast cancer has been largely documented, the contribution of E3 still remains to be completely evaluated. Here, we demonstrate for the first time that E3 acts as a GPR30 antagonist since it was able to inhibit the GPR30-mediated responses such as the rapid ERK activation, the up-regulation of target genes like c-fos and connective tissue growth factor, the proliferative effects observed in ER-negative SkBr3 cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Binding, Competitive / drug effects
Biological Assay
Breast Neoplasms / enzymology
Breast Neoplasms / metabolism*
Breast Neoplasms / pathology*
Cell Line, Tumor
Cell Proliferation / drug effects
Computer Simulation
Connective Tissue Growth Factor / metabolism
Estriol / pharmacology*
Estrogen Receptor alpha / metabolism*
Estrogen Receptor beta / metabolism*
Extracellular Signal-Regulated MAP Kinases / metabolism
Female
Gene Expression Regulation / drug effects
Humans
Phosphorylation / drug effects
Protein Binding / drug effects
Protein Structure, Secondary
Proto-Oncogene Proteins c-fos / metabolism
Receptors, Estrogen
Receptors, G-Protein-Coupled / antagonists & inhibitors*

Substances

CCN2 protein, human
ESR1 protein, human
Estrogen Receptor alpha
Estrogen Receptor beta
GPER1 protein, human
Proto-Oncogene Proteins c-fos
Receptors, Estrogen
Receptors, G-Protein-Coupled
Connective Tissue Growth Factor
Extracellular Signal-Regulated MAP Kinases
Estriol