Role of histamine H4 receptor in breast cancer cell proliferation

VANINA A MEDINA; PABLO G BRENZONI; DIEGO MARTINEL LAMAS; NOELIA MASSARI; MONDILLO CAROLINA; MARIEL A NUÑEZ; PIGNATARO OMAR; ELENA S RIVERA

Frontiers in Bioscience (Elite Edition)

Frontiers in Bioscience

Año: 2011 vol. 1 p. 1042 - 1060

1945-0494

In order to better understand the role of histamine H4 (H4R) receptor in breast cancer, we compared the receptor expression pattern, associated signal transduction pathway, and biological responses in breast cancer cell lines with different malignant characteristics. A different pattern of protein expression was observed in MDA-MB-231 and MCF-7 cells determined by western blot, exhibiting the presence of a diverse range of molecular weight species of the H4R. H4R agonist reduced cyclic adenosine monophosphate (cAMP) formation induced by forskolin only in MCF-7 cells. In MDA-MB-231 cells, H4R agonists significantly decreased cell proliferation, augmented the Annexin-V and TdT-mediated UTP-biotin Nick End labelling (TUNEL) positive cells and produced a 2.5-fold increase in cell senescence. In MCF-7 cells, H4R agonists inhibited proliferation by 50%, increasing the exponential doubling time. This effect was associated to an increase in Annexin-V and TUNEL positive cells, and a 2-fold increase in cell senescence. We conclude that H4R is functionally expressed in human breast cancer cell lines, exhibiting a key role in histamine-mediated biological processes such as cell proliferation, senescence and apoptosis.