title: Enhanced proliferation of human hepatoma cells by PAR-2 agonists via             the ERK/AP-1 pathway.
abstract: 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 immuno-histochemistry, 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-NH2 (P<0.001). The proliferation rate of HepG2 cells treated with trypsin or SLIGKV-NH2 was significantly increased (P<0.001). The percentage of S phase, G2/M phase and the proliferation index (PI) of HepG2 cells treated with trypsin or SLIGKV-NH2 were significantly elevated (P<0.001). The proliferative responses of HepG2 to trypsin and SLIGKV-NH2 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.
authors.affiliation: Department of Gastroenterology, Affiliated Hospital, Logistics College of Chinese People's Armed Police Forces, Tianjin 300162, PR China. xieliqun66@hotmail.com
authors.forename: Liqun
authors.initials: L
authors.lastname: Xie
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zheng
authors.forename: Xuan
authors.initials: X
authors.lastname: Li
authors.forename: Junyan
authors.initials: J
authors.lastname: Zhao
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.forename: Ou
authors.initials: O
authors.lastname: Hai
authors.forename: Fei
authors.initials: F
authors.lastname: Li
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D044464:Receptor, PAR-2 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014357:Trypsin / Q000494:pharmacology
chemical_list: D005419:Flavonoids; D009842:Oligopeptides; D018809:Proliferating Cell Nuclear Antigen; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D044464:Receptor, PAR-2; D018808:Transcription Factor AP-1; C515807:seryl-leucyl-isoleucyl-glycyl-lysyl-valinamide; D048049:Extracellular Signal-Regulated MAP Kinases; D014357:Trypsin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one