Characterization of PAR1 expression in human prostate cancer Free

2017

Introduction and Objectives: Identification of new biomarkers of prostate cancer growth and progression represents a major challenge for development of new treatment. Proteinases activated receptors (PARs) are important members of the G protein-coupled receptors family. The proteolytic cleavage of their extracellular domain by serine proteases like trypsin or thrombin, generates an autoactivating tethered-ligand. Thus, the corresponding activated G proteins trigger a cascade of downstream signaling pathways that lead to diverse cellular outcomes such as changes in calcium level, cell adhesion, cell migration and mitogenesis. The role of proteases in promoting invasion of cancer cells and tumorigenesis have prompted us to investigate the potential role of the thrombin receptor PAR1 in prostate cancer. Methods: Quantitative RT-PCR (qRT-PCR) was used to quantify the mRNA expression level of PAR1 in 40 human prostatic tissues including normal (n=10) and tumor specimens (n=30). The same approach was performed on various prostate cancer cell lines. To assess the role of PAR1 in cell proliferationwe evaluated the effects of thrombin and activating synthetic peptide (AP) at different concentrations. Results: qRT-PCR showed that PAR1 mRNA were up-regulated in human prostate cancer specimens. These results were also observed in prostatic tumor cell lines. In vitro, our results indicate that thrombin and (AP) induce prostate cell lines proliferation in a dose dependent manner. Conclusions: These results underline the importance of PAR1 in prostate cancer. The PAR1 expression profile likely influences cancer cell behaviour. As such PAR1 protein may represent novel target for therapeutic intervention.