title: Inactivation of the 14-3-3 sigma gene is associated with 5' CpG island hypermethylation in human cancers.
abstract: The cell cycle checkpoint plays an important role in maintaining the integrity of cells. Recently, one of the 14-3-3 protein family members, 14-3-3sigma, was shown to be regulated by p53 and to play a role in the G2-M-phase checkpoint. To determine whether 14-3-3sigma is inactivated in human cancers, the methylation status of the 5' region of 14-3-3sigma was investigated in a series of gastric, colorectal, and hepatocellular cancer cell lines. Of 22 cell lines examined, 6 showed aberrant methylation. The methylation status of 14-3-3sigma was found to be correlated with loss of expression, which was restored by 5-aza-2'-deoxycytidine treatment. Furthermore, normal G2 arrest after DNA damage was not demonstrated in the cell lines with methylation. In primary gastric cancers, 14-3-3sigma hypermethylation was observed frequently in 26 of 60 (43%) cases and observed more frequently in poorly differentiated adenocarcinomas (P = 0.0017). Our findings suggest that 14-3-3sigma is inactivated by aberrant methylation of the 5' region in various human cancers and that it might play an important role in the development of undifferentiated gastric cancers.
authors.affiliation: First Department of Internal Medicine, Sapporo Medical University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: F
authors.initials: F
authors.lastname: Itoh
authors.forename: M
authors.initials: M
authors.lastname: Toyota
authors.forename: T
authors.initials: T
authors.lastname: Kikuchi
authors.forename: H
authors.initials: H
authors.lastname: Kakiuchi
authors.forename: K
authors.initials: K
authors.lastname: Imai
mesh_terms: D048948:14-3-3 Proteins; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D000483:Alleles; D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014408:Biomarkers, Tumor; D002453:Cell Cycle / Q000502:physiology; D018899:CpG Islands / Q000235:genetics / Q000502:physiology*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D000077209:Decitabine; D004591:Electrophoresis, Polyacrylamide Gel; D005092:Exonucleases; D005095:Exoribonucleases; D005453:Fluorescence; D016195:G2 Phase / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects / Q000502:physiology*; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009363:Neoplasm Proteins; D009368:Neoplasm Transplantation; D009690:Nucleic Acid Conformation; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism; D013447:Sulfites; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D011506:Proteins; D013447:Sulfites; D016159:Tumor Suppressor Protein p53; D000077209:Decitabine; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human; D001374:Azacitidine; C042345:hydrogen sulfite