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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 12/2010

01-12-2010 | Translational Research and Biomarkers

Jun Activation Domain Binding Protein 1 is Overexpressed from the Very Early Stages of Hepatocarcinogenesis

Authors: Shinichi Yachida, MD, Katsumi Imaida, MD, Masanao Yokohira, MD, Nozomi Hashimoto, MD, Shugo Suzuki, MD, Keiichi Okano, MD, Hisao Wakabayashi, MD, Hajime Maeta, MD, Yasuyuki Suzuki, MD

Published in: Annals of Surgical Oncology | Issue 12/2010

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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 p27Kip1 expression is evident from the very early stages of hepatocarcinogenesis.

Methods

In the present study, expression of p27Kip1 and Jun activation domain binding protein-1 (Jab1), which is a key molecule involved in posttranslational regulation of p27Kip1, 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 p27Kip1 and Jab1 mRNA expression levels (P = 0.0014).

Conclusions

Jab1 expression, as well as p27Kip1 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.
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Metadata
Title
Jun Activation Domain Binding Protein 1 is Overexpressed from the Very Early Stages of Hepatocarcinogenesis
Authors
Shinichi Yachida, MD
Katsumi Imaida, MD
Masanao Yokohira, MD
Nozomi Hashimoto, MD
Shugo Suzuki, MD
Keiichi Okano, MD
Hisao Wakabayashi, MD
Hajime Maeta, MD
Yasuyuki Suzuki, MD
Publication date
01-12-2010
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 12/2010
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-010-1197-7

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