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

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 patterns; 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.

• Authors: Meliha Mehmeti, Roni Allaoui, Caroline Bergenfelz, Lao H Saal, Stephen P Ethier, Martin E Johansson, Karin Jirström, Karin Leandersson
• Journal: Breast cancer research : BCR (Breast Cancer Res) Vol. 17 Pg. 130 (Sep 22 2015) ISSN: 1465-542X [Electronic] England
• PMID: 26392082 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• Receptors, Estrogen
• Receptors, Progesterone
• TLR2 protein, human
• TLR4 protein, human
• Toll-Like Receptor 2
• Toll-Like Receptor 4

Topics

• Breast Neoplasms (genetics)
• Cell Line, Tumor
• Female
• Gene Expression (genetics)
• Humans
• MCF-7 Cells
• NF-kappa B (genetics)
• Receptors, Estrogen (genetics)
• Receptors, Progesterone (genetics)
• Signal Transduction (genetics)
• Toll-Like Receptor 2 (genetics)
• Toll-Like Receptor 4 (genetics)