TGF-beta type I receptor as a possible mediator of the epithelial to mesenchymal transition induced by histamine H4 receptor ligands in MDA-MB-231 breast cancer cells.

MÓNICA A. TÁQUEZ DELGADO, TAMARA E. GALARZA, NORA A. MOHAMAD, GUADALUPE M. VEDOYA, VANINA MEDINA, GABRIELA MARTIN, GRACIELA CRICCO

Amsterdam

Congreso; European Histamine Research Society. XLVI Annual Meeting. 1st joint meeting of the European and Japanese Histamine Research Societies.; 2017

European Histamine Research Society

We have previously demonstrated that histamine induces the epithelial-mesenchymal transition (EMT) program by stimulating the histamine H4 receptor (H4R) in the human mammary carcinoma cell line MDA-MB-231. The H4R ligands increase the expression of the mesenchymal marker vimentin and the nuclear expression of β-catenin and Slug transcription factor, and also cell migration. All these EMT related events were prevented by Src inhibitors. Src is a non receptor tyrosine kinase, which is tightly involved in cell migration. In addition, TGF-β 1 is a recognized inducer of EMT, a critical process for invasion and metastasis.The aim of this work was to investigate whether the EMT induced by H4R ligands could be mediated by TGF-β type I receptor activation.All experiments were performed in RPMI medium without fetal bovine serum. MDA-MB-231 cells treated with H4R ligands and/or the TGF-β type I receptor kinase inhibitor A83-01 (10 μM) were incubated for 24 h. Indirect immunofluorescence and Western blotting studies confirmed the presence of cytoplasmic TGF-β 1 in cells treated with 10 μM of the H4R ligands VUF8430 or clobenpropit. TGF-β 1 levels were not increased when cells received A83-01 + H4R ligands. The H4R ligand mediated increase in vimentin and Slug expression was also blocked by pre-treatment with A83-01 (p