title: Histamine H4 receptor: insights into a potential therapeutic target in breast cancer.
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.
authors.forename: Diego J
authors.initials: DJ
authors.lastname: Martinel Lamas
authors.forename: Elena S
authors.initials: ES
authors.lastname: Rivera
authors.affiliation: Laboratory of Radioisotopes, School of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, Buenos Aires, Argentina 1113, vmedina@ffyb.uba.ar.
authors.forename: Vanina A
authors.initials: VA
authors.lastname: Medina
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D064593:Heterografts; D006632:Histamine / Q000378:metabolism; D006633:Histamine Antagonists / Q000627:therapeutic use; D006801:Humans; D008024:Ligands; D058990:Molecular Targeted Therapy; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011968:Receptors, Histamine / Q000378:metabolism; D000074040:Receptors, Histamine H4
chemical_list: D000970:Antineoplastic Agents; C418607:HRH4 protein, human; D006633:Histamine Antagonists; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D006632:Histamine