title: Involvement of MAPK and PI3K signaling pathway in sterigmatocystin-induced G2 phase arrest in human gastric epithelium cells.
abstract: METHODS
  Sterigmatocystin (ST), a mycotoxin commonly found in foodstuff and feedstuff, has been shown to be a carcinogenic mycotoxin in animal models. Many studies showed that the high level of ST contamination in grains might be related to the high incidence of gastric carcinoma in rural areas of China. However, up to now, the potential effects of ST on human gastric epithelium cells remain largely unknown. In this study, we explored the effects of ST on cell-cycle distribution and the regulatory mechanism in immortalized human gastric epithelium cells (GES-1).
  
  
  RESULTS
  The effects of ST on the cell cycle distribution of GES-1 cells were determined with flow cytometric (FCM) analysis, Giemsa staining and immunofluorescence staining, while that on the expression of related gene-Cdc25C, Cdc2, CyclinB1 and the complex of CyclinB1-Cdc2 were studied with Western blot, reverse transcription polymerase chain reaction (RT-PCR) and immunoprecipitation assay respectively. We found that ST induced GES-1 cells arrested at G2 phase by regulating the expression of Cdc25C, Cdc2, CyclinB1 and the formation of CyclinB1-Cdc2 complex. Further study suggested JNK, ERK and PI3K/AKT/mTOR pathways to be involved in the process of G2 arrest induced by ST. The specific inhibitors of JNK and ERK reversed the role of ST, whereas that of PI3K/AKT/mTOR reinforced the effect of ST on cell-cycle distribution.
  
  
  CONCLUSIONS
  This study demonstrates that JNK, ERK and PI3K/AKT/mTOR pathways participated in the G2 arrest induced by ST through the deregulation of CyclinB1, Cdc2 and Cdc25C. It may play some roles in the gastric carcinogenesis in ST exposure populations.
authors.affiliation: Department of Pathology, The Second Hospital, Hebei Medical University, Shijiazhuang, P R China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xing
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Ling Xiao
authors.initials: LX
authors.lastname: Xing
authors.forename: Yue Hong
authors.initials: YH
authors.lastname: Li
authors.forename: Xia
authors.initials: X
authors.lastname: Yan
authors.forename: Xiang Hong
authors.initials: XH
authors.lastname: Zhang
mesh_terms: D016203:CDC2 Protein Kinase; D002478:Cells, Cultured; D019926:Cyclin B / Q000502:physiology; D056744:Cyclin B1 / Q000502:physiology; D018844:Cyclin-Dependent Kinases; D016195:G2 Phase / Q000187:drug effects*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013241:Sterigmatocystin / Q000633:toxicity*; D020687:cdc25 Phosphatases / Q000502:physiology
chemical_list: C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D013241:Sterigmatocystin; D019869:Phosphatidylinositol 3-Kinases; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases