Inverse expression of Jun activation domain binding protein 1 and cell cycle inhibitor p27Kip1 : influence on proliferation in hepatocellular carcinoma

• Published in: Human pathology Vol. 38; no. 11; pp. 1621 - 1627
• Main Authors: Berg, Jan P, Zhou, Qi, MD, Breuhahn, Kai, PhD, Schirmacher, Peter, MD, Patil, Mohini A., PhD, Chen, Xin, PhD, Schäfer, Nico, MD, Höller, Tobias T, Fischer, Hans-Peter, MD, Büttner, Reinhard, MD, Gütgemann, Ines
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier 01-11-2007
• Subjects: Biological and medical sciences; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Proliferation; COP9 Signalosome Complex; Cyclin-Dependent Kinase Inhibitor p27 - biosynthesis; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Investigative techniques, diagnostic techniques (general aspects); Ki-67 Antigen - biosynthesis; Liver - metabolism; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Peptide Hydrolases - biosynthesis; Tumors; Immunohistochemistry; Hepatocellular carcinoma; Jab1; p27 Kip1; Cell proliferation; KIP1 Gene; p27Kip1; Hepatic disease; Malignant tumor; Liver cancer; Anatomic pathology; Cell cycle; Digestive diseases; Inhibitor; Jab1 protein; Tumor suppressor gene
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2007.03.007

Summary 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 p27Kip1 , a negative cell cycle regulator, correlates inversely with Jab1 expression in HCC ( P = .014). We observed nuclear Jab1 expression in 57% (55/97) and p27Kip1 expression in 32% (31/97) of HCCs. Neither Jab1 nor p27Kip1 nor inverse Jab1 and p27Kip1 expression correlated with clinicopathological parameters. However, HCCs lacking p27Kip1 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 p27Kip1 protein levels. We conclude that Jab1 expression may lead to down-regulation of the negative cell cycle regulator p27Kip1 , pointing to a possible mechanism that promotes hepatocarcinogenesis.