title: 14-3-3σ mediates G2-M arrest produced by 5-aza-2'-deoxycytidine and possesses a tumor suppressor role in endometrial carcinoma cells.
abstract: OBJECTIVE
  To determine the effect of 5-aza-2'-deoxycytidine (DAC) on human endometrial carcinoma cell (HECC) oncogenicity and demonstrate a molecular mechanism by which DAC modulates HECC oncogenicity.
  
  
  METHODS
  The effect of DAC was tested on HECC RL95-2, AN3, Ishikawa and ECC1 cells. The role of 14-3-3σ on HECC oncogenicity in response to DAC treatment was evaluated in RL95-2 and AN3 cells after forced expression or silencing of 14-3-3σ gene expression.
  
  
  RESULTS
  Treatment of HECC with DAC produced non-cytotoxic cell growth inhibition and G2/M cell cycle arrest. This effect was strongly correlated with increased expression of p21 and 14-3-3σ. Silencing of 14-3-3σ induced cellular proliferation and reduced the effect of DAC on cell cycle arrest in G2/M phases. Conversely, forced expression of 14-3-3σ showed the opposite effect. Furthermore, forced expression of 14-3-3σ in human endometrial cell lines reduced cell growth and colony formation.
  
  
  CONCLUSIONS
  We suggest that 14-3-3σ in HECC suppresses cell proliferation and mediates DAC induced G2/M arrest and inhibition of cell proliferation in HECC.
authors: Liggins Institute, Auckland University, Auckland, New Zealand. m.steiner@auckland.ac.nz
authors: Michael
authors: M
authors: Steiner
authors: Brett
authors: B
authors: Clark
authors: Jian-Zhong
authors: JZ
authors: Tang
authors: Tao
authors: T
authors: Zhu
authors: Peter E
authors: PE
authors: Lobie
mesh_terms: D048948:14-3-3 Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D048708:Cell Growth Processes / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005092:Exonucleases / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D005095:Exoribonucleases; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000187:drug effects; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D014162:Transfection
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D000077209:Decitabine; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human; D001374:Azacitidine