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4 results on '"SKBR3"'

1. The Peptide ERα17p Is a GPER Inverse Agonist that Exerts Antiproliferative Effects in Breast Cancer Cells

Author

Rosamaria Lappano, Christophe Mallet, Bruno Rizzuti, Fedora Grande, Giulia Raffaella Galli, Cillian Byrne, Isabelle Broutin, Ludivine Boudieu, Alain Eschalier, Yves Jacquot, and Marcello Maggiolini

Subjects
peptide, anti-proliferation, inverse agonist, desensitizer, GPER, SkBr3, breast cancer, Cytology, QH573-671
Abstract

The inhibition of the G protein-coupled estrogen receptor (GPER) offers promising perspectives for the treatment of breast tumors. A peptide corresponding to part of the hinge region/AF2 domain of the human estrogen receptor α (ERα17p, residues 295–311) exerts anti-proliferative effects in various breast cancer cells including those used as triple negative breast cancer (TNBC) models. As preliminary investigations have evoked a role for the GPER in the mechanism of action of this peptide, we focused our studies on this protein using SkBr3 breast cancer cells, which are ideal for GPER evaluation. ERα17p inhibits cell growth by targeting membrane signaling. Identified as a GPER inverse agonist, it co-localizes with GPER and induces the proteasome-dependent downregulation of GPER. It also decreases the level of pEGFR (phosphorylation of epidermal growth factor receptor), pERK1/2 (phosphorylation of extracellular signal-regulated kinase), and c-fos. ERα17p is rapidly distributed in mice after intra-peritoneal injection and is found primarily in the mammary glands. The N-terminal PLMI motif, which presents analogies with the GPER antagonist PBX1, reproduces the effect of the whole ERα17p. Thus, this motif seems to direct the action of the entire peptide, as highlighted by docking and molecular dynamics studies. Consequently, the tetrapeptide PLMI, which can be claimed as the first peptidic GPER disruptor, could open new avenues for specific GPER modulators.

Published
2019
Full Text
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2. The Peptide ERα17p Is a GPER Inverse Agonist that Exerts Antiproliferative Effects in Breast Cancer Cells

Author

Ludivine Boudieu, Yves Jacquot, Christophe Mallet, Rosamaria Lappano, Marcello Maggiolini, Cillian Byrne, Isabelle Broutin, Bruno Rizzuti, Alain Eschalier, Fedora Grande, Giulia Raffaella Galli, Università della Calabria [Arcavacata di Rende] (Unical), CHU Clermont-Ferrand, Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Cibles Thérapeutiques et conception de médicaments (CiTCoM - UMR 8038), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), and Gestionnaire, Hal Sorbonne Université

Subjects
0301 basic medicine, Estrogen receptor, Apoptosis, Triple Negative Breast Neoplasms, inverse agonist, Receptors, G-Protein-Coupled, Mice, 0302 clinical medicine, SkBr3, Epidermal growth factor receptor, Extracellular Signal-Regulated MAP Kinases, lcsh:QH301-705.5, Triple-negative breast cancer, biology, Chemistry, General Medicine, GPER, peptide, 3. Good health, ErbB Receptors, Molecular Docking Simulation, Receptors, Estrogen, desensitizer, SKBR3, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030220 oncology & carcinogenesis, Female, medicine.symptom, Proto-Oncogene Proteins c-fos, hormones, hormone substitutes, and hormone antagonists, Proteasome Endopeptidase Complex, [SDV.CAN]Life Sciences [q-bio]/Cancer, Molecular Dynamics Simulation, Article, src Homology Domains, anti-proliferation, 03 medical and health sciences, breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Downregulation and upregulation, Cell Line, Tumor, medicine, Animals, Humans, Inverse agonist, Cell Proliferation, GRB2 Adaptor Protein, Cell Membrane, Estrogen Receptor alpha, Peptide Fragments, Enzyme Activation, 030104 developmental biology, lcsh:Biology (General), Mechanism of action, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Cancer research, biology.protein
Abstract

The inhibition of the G protein-coupled estrogen receptor (GPER) offers promising perspectives for the treatment of breast tumors. A peptide corresponding to part of the hinge region/AF2 domain of the human estrogen receptor &alpha, (ER&alpha, 17p, residues 295&ndash, 311) exerts anti-proliferative effects in various breast cancer cells including those used as triple negative breast cancer (TNBC) models. As preliminary investigations have evoked a role for the GPER in the mechanism of action of this peptide, we focused our studies on this protein using SkBr3 breast cancer cells, which are ideal for GPER evaluation. ER&alpha, 17p inhibits cell growth by targeting membrane signaling. Identified as a GPER inverse agonist, it co-localizes with GPER and induces the proteasome-dependent downregulation of GPER. It also decreases the level of pEGFR (phosphorylation of epidermal growth factor receptor), pERK1/2 (phosphorylation of extracellular signal-regulated kinase), and c-fos. ER&alpha, 17p is rapidly distributed in mice after intra-peritoneal injection and is found primarily in the mammary glands. The N-terminal PLMI motif, which presents analogies with the GPER antagonist PBX1, reproduces the effect of the whole ER&alpha, 17p. Thus, this motif seems to direct the action of the entire peptide, as highlighted by docking and molecular dynamics studies. Consequently, the tetrapeptide PLMI, which can be claimed as the first peptidic GPER disruptor, could open new avenues for specific GPER modulators.

Published
2019

3. miR-338-3p Is Regulated by Estrogens through GPER in Breast Cancer Cells and Cancer-Associated Fibroblasts (CAFs)

Author

Maria Luisa Panno, Francesca Cirillo, Rosamaria Lappano, Anna Maria Miglietta, Francesca Giordano, Maria Francesca Santolla, Anna Sebastiani, Damiano Cosimo Rigiracciolo, Adele Vivacqua, Marianna Talia, Marcello Maggiolini, and Giulia Raffaella Galli

Subjects
0301 basic medicine, Cell type, Estrogen receptor, Biology, Article, 03 medical and health sciences, breast cancer, 0302 clinical medicine, Cyclin D1, Breast cancer, microRNA, medicine, skin and connective tissue diseases, lcsh:QH301-705.5, c-Fos, CAFs, miR-338-3p, General Medicine, GPER, medicine.disease, 030104 developmental biology, lcsh:Biology (General), SKBR3, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, estrogens
Abstract

Estrogens acting through the classic estrogen receptors (ERs) and the G protein estrogen receptor (GPER) regulate the expression of diverse miRNAs, small sequences of non-coding RNA involved in several pathophysiological conditions, including breast cancer. In order to provide novel insights on miRNAs regulation by estrogens in breast tumor, we evaluated the expression of 754 miRNAs by TaqMan Array in ER-negative and GPER-positive SkBr3 breast cancer cells and cancer-associated fibroblasts (CAFs) upon 17&beta, estradiol (E2) treatment. Various miRNAs were regulated by E2 in a peculiar manner in SkBr3 cancer cells and CAFs, while miR-338-3p displayed a similar regulation in both cell types. By METABRIC database analysis we ascertained that miR-338-3p positively correlates with overall survival in breast cancer patients, according to previous studies showing that miR-338-3p may suppress the growth and invasion of different cancer cells. Well-fitting with these data, a miR-338-3p mimic sequence decreased and a miR-338-3p inhibitor sequence rescued the expression of genes and the proliferative effects induced by E2 through GPER in SkBr3 cancer cells and CAFs. Altogether, our results provide novel evidence on the molecular mechanisms by which E2 may regulate miR-338-3p toward breast cancer progression.

Published
2018

4. The Peptide ERα17p Is a GPER Inverse Agonist that Exerts Antiproliferative Effects in Breast Cancer Cells.

Author

Lappano R, Mallet C, Rizzuti B, Grande F, Galli GR, Byrne C, Broutin I, Boudieu L, Eschalier A, Jacquot Y, and Maggiolini M

Subjects
Animals, Apoptosis drug effects, Cell Line, Tumor, Cell Membrane drug effects, Cell Membrane metabolism, Cell Proliferation drug effects, Enzyme Activation drug effects, ErbB Receptors metabolism, Estrogen Receptor alpha chemistry, Extracellular Signal-Regulated MAP Kinases metabolism, Female, GRB2 Adaptor Protein chemistry, GRB2 Adaptor Protein metabolism, Humans, Mice, Molecular Docking Simulation, Molecular Dynamics Simulation, Peptide Fragments chemistry, Proteasome Endopeptidase Complex metabolism, Proto-Oncogene Proteins c-fos metabolism, Receptors, Estrogen metabolism, Receptors, G-Protein-Coupled metabolism, src Homology Domains, Peptide Fragments pharmacology, Receptors, G-Protein-Coupled agonists, Triple Negative Breast Neoplasms pathology
Abstract

The inhibition of the G protein-coupled estrogen receptor (GPER) offers promising perspectives for the treatment of breast tumors. A peptide corresponding to part of the hinge region/AF2 domain of the human estrogen receptor α (ERα17p, residues 295-311) exerts anti-proliferative effects in various breast cancer cells including those used as triple negative breast cancer (TNBC) models. As preliminary investigations have evoked a role for the GPER in the mechanism of action of this peptide, we focused our studies on this protein using SkBr3 breast cancer cells, which are ideal for GPER evaluation. ERα17p inhibits cell growth by targeting membrane signaling. Identified as a GPER inverse agonist, it co-localizes with GPER and induces the proteasome-dependent downregulation of GPER. It also decreases the level of pEGFR (phosphorylation of epidermal growth factor receptor), pERK1/2 (phosphorylation of extracellular signal-regulated kinase), and c-fos. ERα17p is rapidly distributed in mice after intra-peritoneal injection and is found primarily in the mammary glands. The N-terminal PLMI motif, which presents analogies with the GPER antagonist PBX1, reproduces the effect of the whole ERα17p. Thus, this motif seems to direct the action of the entire peptide, as highlighted by docking and molecular dynamics studies. Consequently, the tetrapeptide PLMI, which can be claimed as the first peptidic GPER disruptor, could open new avenues for specific GPER modulators.

Published
2019
Full Text
View/download PDF

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