To investigate the expression and role of PAR-2 in the proliferation of the human hepatoma cell line HepG2, PAR-2 protein and mRNA expression were evaluated by immunohistochemistry, immunofluorescence and RT-PCR analysis. The signaling pathways downstream of PAR-2 activation that lead to hepatoma cell proliferation were analyzed. The results showed that PAR-2 is expressed in human hepatoma cells and PAR-2 mRNA expression was found to be upregulated in cells treated with trypsin or SLIGKV-NH 2

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... <0.001). The proliferation rate of HepG2 cells treated with trypsin or SLIGKV-NH 2 was significantly increased (P<0.001). The percentage of S phase, G 2 /M phase and the proliferation index (PI) of HepG2 cells treated with trypsin or SLIGKV-NH 2 were significantly elevated (P<0.001). The proliferative responses of HepG2 to trypsin and SLIGKV-NH 2 were associated with the upregulation of c-fos and PCNA, which were significantly blocked by PD98059 pretreatment. In conclusion, our results indicate that PAR-2 enhances proliferation of human hepatoma cells possibly via the ERK/ AP-1 pathway.