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Bradykinin enhances cell migration in human prostate cancer cells through B2 receptor/PKCδ/c‐Src dependent signaling pathway
Author(s) -
Yu HsinShan,
Lin TienHuang,
Tang ChihHsin
Publication year - 2013
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22544
Subject(s) - bradykinin , rottlerin , proto oncogene tyrosine protein kinase src , cancer research , protein kinase c , prostate cancer , transfection , endocrinology , medicine , signal transduction , chemistry , receptor , biology , cancer , cell culture , microbiology and biotechnology , genetics
BACKGROUND Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to the bone. Bradykinin (BK) is an inflammatory mediator, and shows elevated levels in regions of severe injury and inflammatory diseases. The aim of this study was to investigate whether Bradykinin is associated with migration of prostate cancer cells. METHODS Cancer cells migration activity was examined using the Transwell assay. The c‐Src and PKCδ phosphorylation was examined by using Western blot method. The qPCR was used to examine the mRNA expression of metalloproteinase. A transient transfection protocol was used to examine NF‐κB activity. RESULTS We found that bradykinin increased the chemomigration and the expression of MMP‐9 of human prostate cancer cells. Bradykinin‐mediated chemomigration and metalloproteinase expression was attenuated by PKCδ inhibitor (rottlerin), PKCδ siRNA, c‐Src inhibitor (PP2) and c‐Src mutant. Activations of PKCδ, c‐Src and NF‐κB pathways after bradykinin treatment was demonstrated, and bradykinin‐induced expression of metalloproteinase and chemomigration activity was inhibited by the specific inhibitor and mutant of PKCδ, c‐Src, and NF‐κB cascades. CONCLUSIONS This study showed for the first time that the bradykinin mediates migration of human prostate cancer cells. One of the mechanisms underlying bradykinin directed migration was transcriptional up‐regulation of MMP‐9 and activation of B2 receptor, PKCδ, c‐Src, and NF‐κB pathways. Prostate 73: 89–100, 2013. © 2012 Wiley Periodicals, Inc.