title: [The roles of activated protein-1 and cell cycle protein in silica-induced cell cycle changes].
abstract: OBJECTIVE
  To investigate the roles of cyclin D1 and CDK4 in the cell cycle changes of human embryonic lung fibroblasts (HELFs) exposed to silica.
  
  
  METHODS
  HELFs were divided into 4 groups: control group, curcumin (20 µmol/L for 1 h) group, silica (200 µg/ml for 24 h) group and curcumin plus silica group, i.e. after exposure to 20 µmol/L curcumin for 1h, the HELFs were treated with 200 µg/ml silica for 24 h. Western blot and Immunofluorescence assays were utilized to detect the expression levels of cyclin D1, CDK4 and E2F1/4. Flow cytometry was used to detect the cell cycle progression, the RNA transfection technique was used to investigate the silica-induced signal pathway and the roles of which in silica-induced cell cycle changes.
  
  
  RESULTS
  The expression levels of cyclin D1 and CDK4 significantly increased and the expression level of E2F-4 decreased obviously, but the expression level of E2F-1 did not significantly change in silica group. The proportion of G1 phase cells obviously decreased and the proportion of S phase cells significantly increased in silica group, as compared with control group (P < 0.05). When suppressing the expression of cyclin D1 or CDK4, the proportions of cells in G1 phase in anti-D1 plus silica group and anti-K4 plus silica group did not obviously change, as compared with control group. When suppressing AP-1 activity, the cyclin D1 and CDK4 expression levels decreased and the E2F-4 expression level increased in curcumin plus silica group, as compared with silica group.
  
  
  CONCLUSIONS
  The results of present suggested that 200 µg/ml silica could induce the high expression of cyclin D1 and CDK4 and the low expression of E2F-4, resulting in the cell cycle changes by AP-1/cyclin D1 pathway in HELFs.
authors.affiliation: National Institute of Occupation Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
authors.forename: Xiao-wei
authors.initials: XW
authors.lastname: Jia
authors.forename: Bing-ci
authors.initials: BC
authors.lastname: Liu
authors.forename: Meng
authors.initials: M
authors.lastname: Ye
authors.forename: Hai-feng
authors.initials: HF
authors.lastname: Liu
authors.forename: Feng-mei
authors.initials: FM
authors.lastname: Zhang
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism*; D050704:E2F4 Transcription Factor / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D016193:G1 Phase; D006801:Humans; D011791:Quartz / Q000009:adverse effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014162:Transfection
chemical_list: C530104:CCND1 protein, human; D050704:E2F4 Transcription Factor; C493762:E2F4 protein, human; D018808:Transcription Factor AP-1; D019938:Cyclin D1; D011791:Quartz; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4