Agonists and knockdown of estrogen receptor β differentially affect invasion of triple-negative breast cancer cells in vitroReport as inadecuate

Agonists and knockdown of estrogen receptor β differentially affect invasion of triple-negative breast cancer cells in vitro - Download this document for free, or read online. Document in PDF available to download.

BMC Cancer

, 16:951

Cell and molecular biology


BackgroundEstrogen receptor β ERβ is expressed in the majority of invasive breast cancer cases, irrespective of their subtype, including triple-negative breast cancer TNBC. Thus, ERβ might be a potential target for therapy of this challenging cancer type. In this in vitro study, we examined the role of ERβ in invasion of two triple-negative breast cancer cell lines.

MethodsMDA-MB-231 and HS578T breast cancer cells were treated with the specific ERβ agonists ERB-041, WAY200070, Liquiritigenin and 3β-Adiol. Knockdown of ERβ expression was performed by means of siRNA transfection. Effects on cellular invasion were assessed in vitro by means of a modified Boyden chamber assay. Transcriptome analyses were performed using Affymetrix Human Gene 1.0 ST microarrays. Pathway and gene network analyses were performed by means of Genomatix and Ingenuity Pathway Analysis software.

ResultsInvasiveness of MBA-MB-231 and HS578T breast cancer cells decreased after treatment with ERβ agonists ERB-041 and WAY200070. Agonists Liquiritigenin and 3β-Adiol only reduced invasion of MDA-MB-231 cells. Knockdown of ERβ expression increased invasiveness of MDA-MB-231 cells about 3-fold. Transcriptome and pathway analyses revealed that ERβ knockdown led to activation of TGFβ signalling and induced expression of a network of genes with functions in extracellular matrix, tumor cell invasion and vitamin D3 metabolism.

ConclusionsOur data suggest that ERβ suppresses invasiveness of triple-negative breast cancer cells in vitro. Whether ERβ agonists might be useful drugs in the treatment of triple-negative breast cancer, has to be evaluated in further animal and clinical studies.

KeywordsEstrogen receptor beta Triple-negative breast cancer Cell culture Invasion AbbreviationsCKCytokeratin

DMEMDulbecco’s modified eagle’s medium

DNADeoxyribonucleic acid

ERβEstrogen receptor beta

FCSFetal calf serum

GOGene ontology

PCRPolymerase chain reaction

qPCRQuantitative polymerase chain reaction

RNARibonucleic acid

RTReverse transcription

siRNAShort interfering ribonucleic acid

TGFβTransforming growth factor beta

TNBCTriple negative breast cancer

Electronic supplementary materialThe online version of this article doi:10.1186-s12885-016-2973-y contains supplementary material, which is available to authorized users.

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Author: Susanne Schüler-Toprak - Julia Häring - Elisabeth C. Inwald - Christoph Moehle - Olaf Ortmann - Oliver Treeck


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