Inverse expression of Jun activation domain binding protein 1 and cell cycle inhibitor p27Kip1: influence on proliferation in hepatocellular carcinoma.
Recently, the functional role of Jun activation domain binding protein 1 (Jab1) as a putative novel oncogene in hepatocellular carcinoma (HCC) has been postulated. We show that expression of p27(Kip1), a negative cell cycle regulator, correlates inversely with Jab1 expression in HCC (P = .014). We observed nuclear Jab1 expression in 57% (55/97) and p27(Kip1) expression in 32% (31/97) of HCCs. Neither Jab1 nor p27(Kip1) nor inverse Jab1 and p27(Kip1) expression correlated with clinicopathological parameters. However, HCCs lacking p27(Kip1) with increased proliferative activity were frequently found to express Jab1 (P = .048). Normal liver tissue, cirrhosis, and tumor-like lesions (focal nodular hyperplasia, dysplastic nodules in cirrhotic liver) showed no significant Jab1 expression. In transfection studies in the hepatoma cell line Huh 7, Jab1 overexpression resulted in reduced p27(Kip1) protein levels. We conclude that Jab1 expression may lead to down-regulation of the negative cell cycle regulator p27(Kip1), pointing to a possible mechanism that promotes hepatocarcinogenesis.
Berg
Jan P
JP
Institute of Pathology, University of Bonn, D-53127 Bonn, Germany.
Zhou
Qi
Q
Breuhahn
Kai
K
Schirmacher
Peter
P
Patil
Mohini A
MA
Chen
Xin
X
Schäfer
Nico
N
Höller
Tobias T
TT
Fischer
Hans-Peter
HP
Büttner
Reinhard
R
Gütgemann
Ines
I
D000075686:COP9 Signalosome Complex; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D010447:Peptide Hydrolases / Q000096:biosynthesis*
D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D050760:Cyclin-Dependent Kinase Inhibitor p27; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex