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Open Access 01-12-2015 | Research article

Expression of functional toll like receptor 4 in estrogen receptor/progesterone receptor-negative breast cancer

Authors: Meliha Mehmeti, Roni Allaoui, Caroline Bergenfelz, Lao H. Saal, Stephen P. Ethier, Martin E. Johansson, Karin Jirström, Karin Leandersson

Published in: Breast Cancer Research | Issue 1/2015

Abstract

Introduction

Toll-like receptors (TLRs) are a family of pattern recognition receptors that are expressed on cells of the innate immune system. The ligands can be pathogen derived (pathogen associated molecular patterns; PAMPs) or endogenous (damage associated molecular patters; DAMPs) that when bound induces activation of nuclear factor kappa B (NF-κB) and transcription of pro-inflammatory genes. TLRs have also been discovered in various malignant cell types, but with unknown function.

Methods

In this study we performed a detailed analysis of TLR and co-receptor expression pattern and function in breast cancer. Expression patterns were examined using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) on three estrogen receptor-positive (ER⁺) and four estrogen receptor/progesterone receptor-negative (ER⁻/PR⁻; ER/PR-negative) breast cancer cell lines, and a breast cancer cohort consisting of 144 primary breast cancer samples. The function was investigated using in vitro assays comprising PAMP/DAMP-stimulation, downstream signaling and TLR-silencing experiments.

Results

We found that TLR4 was expressed in a biologically active form and responded to both PAMPs and DAMPs primarily in ER/PR-negative breast cancers. Stimulation of TLR2/4 in vitro induced expression of pro-inflammatory genes and a gene expression analysis of primary breast cancers showed a strong correlation between TLR4 expression and expression of pro-inflammatory mediators. In line with this, TLR4 protein expression correlated with a decreased survival.

Conclusions

These findings suggest that TLR4 is expressed in a functional form in ER/PR-negative breast cancers. Studies regarding TLR4-antagonist therapies should be focusing on ER/PR-negative breast cancer particularly.

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Title: Expression of functional toll like receptor 4 in estrogen receptor/progesterone receptor-negative breast cancer
Authors: Meliha Mehmeti
Roni Allaoui
Caroline Bergenfelz
Lao H. Saal
Stephen P. Ethier
Martin E. Johansson
Karin Jirström
Karin Leandersson
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Breast Cancer Research / Issue 1/2015
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/s13058-015-0640-x

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