title: Jun activation domain binding protein 1 is overexpressed from the very early stages of hepatocarcinogenesis.
abstract: BACKGROUND
  As is known for many types of human cancers, the hepatocellular carcinoma (HCC) associated with chronic liver disease shows an obvious multistage process of tumor progression. Despite the demonstrated importance of cell-cycle regulators in tumor biology, there have only been a few studies of their role in multistep hepatocarcinogenesis. Recently, we reported that a high level of p27(Kip1) expression is evident from the very early stages of hepatocarcinogenesis.
  
  
  METHODS
  In the present study, expression of p27(Kip1) and Jun activation domain binding protein-1 (Jab1), which is a key molecule involved in posttranslational regulation of p27(Kip1), was evaluated in surgically resected specimens of 8 dysplastic nodules (DNs), 16 early HCCs, and 126 classical HCCs.
  
  
  RESULTS
  Immunohistochemistry revealed no Jab1 expression in the majority of hepatocytes in noncancerous normal liver tissue and cases of chronic hepatitis or cirrhosis. In contrast, Jab1 was overexpressed in 50% (4/8) and 50% (8/16) of DNs and early HCCs, respectively, and the labeling index was increased in line with the degree of loss of differentiation in classical HCCs. Real-time quantitative reverse transcription polymerase chain reactions revealed the Jab1 mRNA levels in all tested early and well-differentiated HCCs to be increased compared with matched nontumorous liver specimens. The Spearman coefficient pointed to a high correlation between p27(Kip1) and Jab1 mRNA expression levels (P = 0.0014).
  
  
  CONCLUSIONS
  Jab1 expression, as well as p27(Kip1) upregulation, is evident from the very early stages of hepatocarcinogenesis, suggesting that Jab1 could be a diagnostic marker and a treatment target for precancerous lesions and early HCCs.
authors.affiliation: Department of Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan. syachida@kms.ac.jp
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yachida
authors.forename: Katsumi
authors.initials: K
authors.lastname: Imaida
authors.forename: Masanao
authors.initials: M
authors.lastname: Yokohira
authors.forename: Nozomi
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Shugo
authors.initials: S
authors.lastname: Suzuki
authors.forename: Keiichi
authors.initials: K
authors.lastname: Okano
authors.forename: Hisao
authors.initials: H
authors.lastname: Wakabayashi
authors.forename: Hajime
authors.initials: H
authors.lastname: Maeta
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D000368:Aged; D000075686:COP9 Signalosome Complex; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex