title: P53 suppresses expression of the 14-3-3 gamma oncogene.
abstract: BACKGROUND
  14-3-3 proteins are a family of highly conserved proteins that are involved in a wide range of cellular processes. Recent evidence indicates that some of these proteins have oncogenic activity and that they may promote tumorigenesis. We previously showed that one of the 14-3-3 family members, 14-3-3 gamma, is over expressed in human lung cancers and that it can induce transformation of rodent cells in vitro.
  
  
  METHODS
  qRTPCR and Western blot analysis were performed to examine 14-3-3 gamma expression in non-small cell lung cancers (NSCLC). Gene copy number was analyzed by qPCR. P53 mutations were detected by direct sequencing and also by western blot. CHIP and yeast one hybrid assays were used to detect p53 binding to 14-3-3 gamma promoter.
  
  
  RESULTS
  Quantitative rtPCR results showed that the expression level of 14-3-3 gamma was elevated in the majority of NSCLC that we examined which was also consistent with protein expression. Further analysis of the expression pattern of 14-3-3 gamma in lung tumors showed a correlation with p53 mutations suggesting that p53 might suppress 14-3-3 gamma expression. Analysis of the gamma promoter sequence revealed the presence of a p53 consensus binding motif and in vitro assays demonstrated that wild-type p53 bound to this motif when activated by ionizing radiation. Deletion of the p53 binding motif eliminated p53's ability to suppress 14-3-3 gamma expression.
  
  
  CONCLUSIONS
  Increased expression of 14-3-3 gamma in lung cancer coincides with loss of functional p53. Hence, we propose that 14-3-3 gamma's oncogenic activities cooperate with loss of p53 to promote lung tumorigenesis.
authors.affiliation: Arizona Cancer Center, Department of Cellular & Molecular Medicine, University of Arizona, Tucson, Arizona 85724, USA.
authors.forename: Vijayababu M
authors.initials: VM
authors.lastname: Radhakrishnan
authors.forename: Charles W
authors.initials: CW
authors.lastname: Putnam
authors.forename: Wenqing
authors.initials: W
authors.lastname: Qi
authors.forename: Jesse D
authors.initials: JD
authors.lastname: Martinez
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism; D016384:Consensus Sequence; D005784:Gene Amplification; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009857:Oncogenes; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53