title: P115 promotes growth of gastric cancer through interaction with macrophage migration inhibitory factor.
abstract: OBJECTIVE
  To investigate the role of P115 in the proliferation of gastric cancer cells and the mechanism involved.
  
  
  METHODS
  The RNA and protein level of P115 and macrophage migration inhibitory factor (MIF) in gastric cancer and normal gastric tissue/cells were measured and the effect of P115 on cell proliferation was assessed. The role of P115 in cell cycle checkpoints was investigated and the related proteins and signaling pathways, such as cyclin D1, Mcm2, p53, PCNA as well as the MAPK signaling pathway were determined. The interaction between P115 and MIF and the effect of P115 on MIF secretion were examined. The data were analyzed via one-way ANOVA comparisons between groups and P < 0.05 was considered significant.
  
  
  RESULTS
  P115 and MIF were both specifically expressed in gastric cancer tissues compared with normal gastric mucosa (both P < 0.01). The mRNA and protein levels of P115 and MIF in gastric cancer cell lines MKN-28 and BGC-823 were higher than in the human gastric epithelial cell line GES-1 (both P < 0.01). In MKN-28 and BGC-823 cell lines, P115 promoted cell proliferation and G0-G1 to S phase transition. In addition, several cell cycle-related regulators, including cyclin D1, Mcm2, PCNA, pERK1/2 and p53 were up-regulated by P115. Furthermore, the interaction between P115 and MIF was confirmed by co-immunoprecipitation assay. ELISA showed that P115 stimulated the secretion of MIF into the culture supernatant (P < 0.01) and the compensative expression of MIF in cells was observed by Western blotting.
  
  
  CONCLUSIONS
  P115 promotes proliferation of gastric cancer cells through an interaction with MIF.
authors.affiliation: Xiu-Jun Li, Yong-Fen Yi, Department of Pathology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xiu-Jun
authors.initials: XJ
authors.lastname: Li
authors.affiliation: Xiu-Jun Li, Yong-Fen Yi, Department of Pathology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Xiu-Jun Li, Yong-Fen Yi, Department of Pathology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yong-Fen
authors.initials: YF
authors.lastname: Yi
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D000077614:Golgi Matrix Proteins; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D000077614:Golgi Matrix Proteins; D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D033921:Vesicular Transport Proteins; C091580:vesicular transport factor p115; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
keywords: Gastric cancer; Migration inhibitory factor; P115; Proliferation; Protein interaction