Expression of urotensin II and its receptor in human lung adenocarcinoma A549 cells and the effect of urotensin II on lung adenocarcinoma growth in vitro and in vivo.

Urotensin II (UII), originally identified from fish urophysis, is a potent vasoactive peptide and an endogenous ligand for an orphan G protein-coupled receptor GPR14, now named as urotensin II receptor (UT-R). In this study, we investigated the mRNA and protein expressions of UII and its receptor (UT-R) in human lung adenocarcinoma A549 cells, and the effect of exogenous UII on the proliferation of A549 cells in vitro and in vivo. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis showed that both mRNAs and proteins of UII and UT-R were obviously expressed in human lung adenocarcinoma A549 cells. Immunohistochemical analysis showed that UII peptide was mainly expressed in the cyto-plasm, and UT-R protein was expressed on the cytomembrane and also in the cytoplasm. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) analysis demonstrated that treatment with different concentrations of human UII (10(-9), 10(-8), 10(-7) and 10(-6) M) for 48 h significantly increased the number of A549 cells. The effect of UII at the concentration of 10(-7) M on the proliferation of A549 cells is most pronounced. Nude mice bearing human lung adenocarcinoma A549 cells treated with UII showed a significant increase in tumor volume and tumor weight compared with control group. These findings suggest that UII may contribute to the pathogenesis of human lung adenocarcinoma as an autocrine/paracrine growth stimulating factor.