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Histamine H4 receptor: insights into a potential therapeutic target in breast cancer

Diego J. Martinel Lamas1,2,Elena S. Rivera1,Vanina A. Medina1,2,*
1
Laboratory of Radioisotopes, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, 1113, Argentina
2
Institute for Biomedical Research (BIOMED CONICET-UCA), Laboratory of Cellular and Molecular Biology, School of Medical Sciences, Pontifical Catholic University of Argentina (UCA), Buenos Aires, Argentina
DOI: 10.2741/S420 Volume 7 Issue 1, pp.1-9
Published: 01 June 2015
(This article belongs to the Special Issue Histamine revisited: the H4 receptor in health and disease)
*Corresponding Author(s):  
Vanina A. Medina
E-mail:  
vmedina@ffyb.uba.ar
Abstract

Breast cancer is the second most common cancer worldwide, and the leading cause of cancer death in women. Several studies underlined the critical role of histamine in breast cancer development and progression. This review addresses the latest evidence regarding the involvement of histamine and histamine receptors in breast cancer, focusing particularly in the histamine H4 receptor (H4R). Histamine concentration in breast cancer tissues was found to be higher than that in normal tissues of healthy controls by means of an increase in the activity of histidine decarboxylase (HDC), the enzyme involved in histamine production. The expression of H4R in different experimental models and human biopsies, the associated biological responses, as well as the in vivo treatment of experimental tumors with H4R ligands is reviewed. Evidence demonstrates that the H4R exhibits a key role in histamine-mediated biological processes such as cell proliferation, senescence and apoptosis in breast cancer. The polymorphisms of the H4R and HDC genes and their association with breast cancer risk and malignancy reinforce the critical (patho)physiological role of H4R in breast cancer. In addition, H4R agonists display anti-tumor effects in vivo in a triple negative breast cancer model. The findings support the exploitation of the H4R as a molecular target for breast cancer drug development.

Key words

Human Breast Cancer, Histamine H4 Receptor, Proliferation, H4R ligands, Experimental Tumor, Histamine, Review

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Diego J. Martinel Lamas, Elena S. Rivera, Vanina A. Medina. Histamine H4 receptor: insights into a potential therapeutic target in breast cancer. Frontiers in Bioscience-Scholar. 2015. 7(1); 1-9.