title: Hypomethylation of the 14-3-3σ promoter leads to increased expression in non-small cell lung cancer.
abstract: The 14-3-3 proteins are a set of seven highly conserved proteins that have recently been implicated in having a role in human tumorigenesis. However, the mechanism by which 14-3-3 proteins may act in this capacity is not well understood. In this study, we examined the expression of one of the 14-3-3 family members, 14-3-3σ, since it was shown previously to be aberrantly altered in human tumors. Using quantitative rtPCR and immunohistochemistry, we found that the expression levels of 14-3-3σ were elevated in the majority of human non-small cell lung cancers (NSCLC) we examined. Surprisingly, we found that the 14-3-3σ gene was hypomethylated in lung tumors relative to normal lung tissue suggesting that decreased DNA methylation resulted in increased expression of 14-3-3σ in NSCLC. We also determined the gene copy number for 14-3-3σ in tumor samples and found no significant correlation with elevated mRNA expression. And also no mutations were found in 14-3-3σ gene. Overall, our data suggest that misregulated expression of 14-3-3σ gene may be due to altered methylation status. © 2011 Wiley-Liss, Inc.
authors.affiliation: Arizona Cancer Center, 1515 N. Campbell Ave, Tucson, Arizona 85724, USA.
authors.forename: Vijayababu M
authors.initials: VM
authors.lastname: Radhakrishnan
authors.forename: Taylor J
authors.initials: TJ
authors.lastname: Jensen
authors.forename: Haiyan
authors.initials: H
authors.lastname: Cui
authors.forename: Bernard W
authors.initials: BW
authors.lastname: Futscher
authors.forename: Jesse D
authors.initials: JD
authors.lastname: Martinez
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D005092:Exonucleases / Q000235:genetics / Q000378:metabolism*; D005095:Exoribonucleases; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human