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

  • Translational Research and Biomarkers
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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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Acknowledgment

This work was supported by a Grant-in-Aid for Scientific Research (15790717, 17790919) from the Ministry of Education, Science and Culture of Japan. We thank Drs. Michiie Sakamoto, Norimasa Koide, and Rie Shibata, Keio University, and Dr. Kousuke Saoo, Kagawa University, for access to archival material. Furthermore, we thank Yukie Yoshino, Mizuho Kuroda, and Aya Hashimoto for expert technical assistance.

Conflicts of Interest

No conflicts of interest exist.

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  1. Shinichi Yachida MD

    Present address: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

Authors and Affiliations

  1. Department of Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Shinichi Yachida MD, Nozomi Hashimoto MD, Keiichi Okano MD, Hisao Wakabayashi MD, Hajime Maeta MD & Yasuyuki Suzuki MD

  2. Department of Pathology and Host-Defense, Kagawa University, Kagawa, Japan

    Katsumi Imaida MD, Masanao Yokohira MD & Nozomi Hashimoto MD

  3. Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Shugo Suzuki MD

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  1. Shinichi Yachida MD
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Yachida, S., Imaida, K., Yokohira, M. et al. Jun Activation Domain Binding Protein 1 is Overexpressed from the Very Early Stages of Hepatocarcinogenesis. Ann Surg Oncol 17, 3386–3393 (2010). https://doi.org/10.1245/s10434-010-1197-7

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  • DOI: https://doi.org/10.1245/s10434-010-1197-7

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