Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Feb 24:10:1207-1216.
doi: 10.2147/OTT.S112165. eCollection 2017.

Toll-like receptor 4 as a predictor of clinical outcomes of estrogen receptor-negative breast cancer in Saudi women

Affiliations

Toll-like receptor 4 as a predictor of clinical outcomes of estrogen receptor-negative breast cancer in Saudi women

Abdelhabib Semlali et al. Onco Targets Ther. .

Abstract

The aim of this study was to investigate the association of the common polymorphisms of Toll-like receptor 4 (TLR-4) with breast cancer development in the Saudi Arabian population. Four TLR-4 polymorphisms (rs2770150, rs10759931, rs10759932, and rs4986790) were studied using 127 breast cancer patients and 117 controls. Relative expression of TLR-4 protein in the breast tumor and the matched normal breast tissues was determined in a large cohort of 70 clinical breast samples in a tissue micro-array format by immunohistochemistry using a specific anti-TLR-4 antibody. Our results demonstrated an increase in TLR-4 expression in estrogen receptor (ER)-, postmenopausal breast cancer patients compared to normal. We also demonstrated that the G allele of single-nucleotide polymorphism rs10759931 was found to be significantly higher in frequency among patients (36.3%) compared to the control group (26.7%), suggesting that this polymorphism is strongly associated with the development of breast cancer in this ethnic population. In addition, the TLR-4 polymorphism rs2770150 was shown to be highly correlated with breast cancer in patients over 48 years of age. The TLR-4 polymorphism rs4986790 was also found to be associated with this malignancy in the ER- patient groups. Our results suggested firstly that the variation in TLR-4 gene expression may influence breast cancer development and secondly a closely linked association between TLR-4 gene polymorphism and ER status. Our study provides support for a better understanding of the implication of TLR-4 polymorphism in breast tumorigenesis and for its eventual use as a cancer biomarker.

Keywords: Saudi population; Toll-like receptor 4; breast cancer; estrogen receptor; innate immunity; single-nucleotide polymorphisms.

PubMed Disclaimer

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Immunohistochemical determination of TLR-4 protein expression in normal and breast cancer tissues. (A) Representative sections (×200) of positive immunostaining of TLR-4 protein expression in normal breast tissues (a and b) and ER− breast cancer tissues (c and d). The staining of samples from ER− premenopausal patients is illustrated in (a and c) and from ER− postmenopausal patients in (b and d). Tissues were immunostained using specific TLR-4 antibodies. (B) TLR-4 positive staining was estimated as follows: 0 point, no positive staining; 1 point, <20% positive staining; 2 points, 21%–50% positive staining; 3 points, 51%–75% positive staining; and 4 points, >75% positive staining. Abbreviations: TLR-4, Toll-like receptor 4; ER, estrogen receptor.

Similar articles

Cited by

References

    1. American Cancer Society Cancer Facts & Figures 2013. [Accessed February 8, 2017]. Available from: https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts....
    1. Yu H, Kortylewski M, Pardoll D. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol. 2007;7(1):41–51. - PubMed
    1. Mavaddat N, Antoniou AC, Easton DF, Garcia-Closas M. Genetic susceptibility to breast cancer. Mol Oncol. 2010;4(3):174–191. - PMC - PubMed
    1. Yu JC, Ding SL, Chang CH, et al. Genetic susceptibility to the development and progression of breast cancer associated with polymorphism of cell cycle and ubiquitin ligase genes. Carcinogenesis. 2009;30(9):1562–1570. - PubMed
    1. de Visser KE, Eichten A, Coussens LM. Paradoxical roles of the immune system during cancer development. Nat Rev Cancer. 2006;6(1):24–37. - PubMed

LinkOut - more resources