Histamine receptor 1 inhibition enhances antitumor therapeutic responses through extracellular signal-regulated kinase (ERK) activation in breast cancer
| Autor: | Patricia Jauregui, Núria Moragas, Paloma Bragado, Leire Recalde-Percaz, Aleix Noguera-Castells, Estel Enreig, Pedro Gascón, Vanessa Almendro, Mario Mancino, Patricia Fernández-Nogueira, Gemma Fuster, Anna López-Plana, Neus Carbó |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Cancer Research Histamine H1 Antagonists Non-Sedating MAP Kinase Signaling System Receptor ErbB-2 Cell Breast Neoplasms 03 medical and health sciences Histamine receptor Basal (phylogenetics) chemistry.chemical_compound Mice 0302 clinical medicine Cell Movement Cell Line Tumor medicine Animals Humans Receptors Histamine H1 Receptor Cell Proliferation Neoplasms Basal Cell Chemistry Cell growth Kinase Drug Synergism Trastuzumab Xenograft Model Antitumor Assays Up-Regulation Gene Expression Regulation Neoplastic 030104 developmental biology medicine.anatomical_structure Oncology Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research MCF-7 Cells Female Terfenadine Histamine |
| Zdroj: | Cancer letters. 424 |
| ISSN: | 1872-7980 |
| Popis: | Histamine receptor 1 (HRH1) belongs to the rhodopsin-like G-protein-coupled receptor family. Its activation by histamine triggers cell proliferation, embryonic development, and tumor growth. We recently established that HRH1 is up-regulated in basal and human epidermal growth factor receptor 2 (HER2)-enriched human breast tumors and that its expression correlates with a worse prognosis. Nevertheless, the functional role of HRH1 in basal and HER2-targeted therapy-resistant breast cancer (BC) progression has not yet been addressed. Using terfenadine, a selective chemical inhibitor of HRH1, we showed that the inhibition of HRH1 activity in basal BC cells leads to sub-G0 cell accumulation, suppresses proliferation, promotes cell motility and triggers the activation of extracellular signal-regulated kinase (ERK) signaling, initiating the mitochondrial apoptotic pathway. Furthermore, HER2-targeted therapy-resistant cells express higher levels of HRH1 and are more sensitive to terfenadine treatment. Moreover, in vivo experiments showed that terfenadine therapy reduced the tumor growth of basal and trastuzumab-resistant BC cells. In conclusion, our results suggest that targeting HRH1 is a promising new clinical approach to consider that could enhance the effectiveness of current therapeutic treatment in patients with basal and BC tumors resistant to HER2-targeted therapies. |
| Databáze: | OpenAIRE |
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