title: [Cross-talk between ERK and NF-kappaB signal transduction pathways in the hepatocytes expressing hepatitis C virus nonstructural protein 3].
abstract: OBJECTIVE
  To explore the cross-talk between extracellular signal-regulated kinase (ERK) and nuclear factor (NF-kappaB) signal transduction pathways in the hepatocytes expressing hepatitis C virus nonstructural protein 3 (HCV NS3).
  
  
  METHODS
  A cell line QSG7701/NS3, which stably expressed HCV NS3 protein, was constructed by transfecting plasmid pcDNA3.1-NS3 into a human immortalized hepatocyte line QSG7701. Before and after QSG7701/NS3 cells were treated by MEK inhibitor PD98059, the phosphorylation level of ERK and the expression of cyclin D1 protein were detected by Western blot; the DNA binding activities of activator protein 1 (AP-1) and NF-kappaB were evaluated with electrophoretic mobility shift assay (EMSA). Cell cycles were measured by flow cytometry (FCM); the effects of PD98059 on the cell proliferation were determined by MTT assay.
  
  
  RESULTS
  HCV NS3 protein could up-regulate the phosphorylation of ERK and the expression level of cyclin D1 in QSG7701 cells. PD98059 could inhibit the cell proliferation mediated by HCV NS3 protein, down-regulate the activities of AP-1 and NF-kappaB, and suppress the expression of cyclin D1.
  
  
  CONCLUSIONS
  The inhibition of ERK can suppress the DNA binding activity of NF-kappaB and the cell proliferation mediated by HCV NS3 protein in a dose-dependent manner. There may be a cross-talk between ERK and NF-kappaB signal transduction pathways, which may exert synergistic action on the proliferation and malignant transformation of hepatocytes.
authors.affiliation: Department of Pathology, College of Basic Medicine, Central South University, Changsha, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.forename: De-Yun
authors.initials: DY
authors.lastname: Feng
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Qiong-Qiong
authors.initials: QQ
authors.lastname: He
authors.forename: Shu-Yan
authors.initials: SY
authors.lastname: Sun
authors.forename: Rui-Xue
authors.initials: RX
authors.lastname: Cheng
mesh_terms: D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D019938:Cyclin D1; D048049:Extracellular Signal-Regulated MAP Kinases; D005419:Flavonoids; D016328:NF-kappa B; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one