title: Identification of the A kinase anchor protein 12 (AKAP12) gene as a candidate tumor suppressor of hepatocellular carcinoma.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is a major health problem, and identification of new tumor-related genes is an urgent task.
  
  
  METHODS
  To detect tumor-related genes effectively, we performed double-combination array analysis, which consisted of an expression array and a single nucleotide polymorphism (SNP) array of a single surgical HCC specimen.
  
  
  RESULTS
  Expression array analysis identified AKAP12 as one of the genes with reduced expression in HCC tissues when compared with non-cancerous adjacent hepatic tissues. In addition, AKAP12 expression levels in tumor tissues from 48 HCC samples were significantly lower (P < 0.001) than those in normal tissues, and the downregulation was significantly correlated with poor overall survival rate (P = 0.003). However, SNP array analysis revealed that locus 6q24-q25 where AKAP12 was located did not show chromosomal deletion. In contrast, hypermethylation in the AKAP12 promoter regions was observed in 41 of 48 HCC samples. We then confirmed that AKAP12 gene re-expression occurs after 5-aza-2'-deoxycytidine (5-aza-dC) treatment through direct sequence analysis of the AKAP12 promoter region in HCC cell lines.
  
  
  CONCLUSIONS
  The current data suggest that AKAP12 is downregulated in cancer tissues through promoter hypermethylation, and may have a role as a candidate tumor suppressor gene for HCC.
authors: Department of Surgery II, Graduate School of Medicine, University of Nagoya, Showa-ku, Nagoya, Japan.
authors: M
authors: M
authors: Hayashi
authors: S
authors: S
authors: Nomoto
authors: M
authors: M
authors: Kanda
authors: Y
authors: Y
authors: Okamura
authors: Y
authors: Y
authors: Nishikawa
authors: S
authors: S
authors: Yamada
authors: T
authors: T
authors: Fujii
authors: H
authors: H
authors: Sugimoto
authors: S
authors: S
authors: Takeda
authors: Y
authors: Y
authors: Kodera
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D017209:Apoptosis; D001374:Azacitidine / Q000031:analogs & derivatives; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D000077209:Decitabine; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D054758:A Kinase Anchor Proteins; C491162:AKAP12 protein, human; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D012333:RNA, Messenger; D000077209:Decitabine; D001374:Azacitidine