Expression of epithelial cell adhesion molecule and proliferating cell nuclear antigen in diethylnitrosamine‑induced hepatocarcinogenesis in mice

Kang,Jin  Seok; Kang,Hwan-Goo; Park,Young-Il; Lee,Hyunjung; Park,Kiho; Lee,Yun-Seok; Kim,Soohee; Ryu,Doug-Young

doi:10.3892/etm.2012.751

Expression of epithelial cell adhesion molecule and proliferating cell nuclear antigen in diethylnitrosamine‑induced hepatocarcinogenesis in mice

Authors:
- Jin Seok Kang
- Hwan-Goo Kang
- Young-Il Park
- Hyunjung Lee
- Kiho Park
- Yun-Seok Lee
- Soohee Kim
- Doug-Young Ryu
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Affiliations: Department of Biomedical Laboratory Science, Namseoul University, Cheonan 330-707, Republic of Korea, Toxicology Laboratory, Toxicology and Residue Chemistry Division, Animal, Plant and Fisheries Quarantine and Inspection Agency, MIFAFF, Anyang 480-757, Republic of Korea, Laboratory of Genomics and Quantitative Real-Time PCR, Biomedical Research Institute, Seoul National University Hospital, Seoul 110-744, Republic of Korea , Department of Health Administration, Namseoul University, Cheonan 330-707, Republic of Korea, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea
Published online on: October 17, 2012 https://doi.org/10.3892/etm.2012.751
Pages: 138-142

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Abstract

To clarify the role of stem cells in hepatocarcinogenesis, the expression of epithelial cell adhesion molecule (EpCAM) and proliferating cell nuclear antigen (PCNA) was investigated in mouse hepatic tumors and embryonic cell lineages. Ten ICR mice were treated with diethylnitrosamine (DEN) at 14 days of age and sacrificed at 36 weeks subsequent to DEN treatment to obtain the hepatic tumors. Mouse embryonic stem cells, hepatic progenitor cells and hepatocyte‑like cells, representing 0, 22 and 40 days of differentiation, respectively, were treated in vitro with DEN at four doses (0, 1, 5 and 15 mM; G1, G2, G3 and G4, respectively) for 24 h and RNA was isolated. A total of 71 hepatic tumors were obtained from the DEN-treated mice. EpCAM expression was increased mainly in hepatic tumor cells, although it was also detected in the surrounding visually normal cells. Double staining showed that EpCAM and PCNA were co-expressed in numerous tumor cells. In vitro, EpCAM expression was significantly different for G4 at day 0 (P<0.01) and for G2, G3 and G4 at day 40 (P<0.01) compared with the control (G1) at the corresponding time-point. PCNA expression was significantly different for G3 and G4 at day 0 (P<0.01), for G2, G3 and G4 at day 22 (P<0.01) and for G2 at day 40 (P<0.01) compared with G1 at the corresponding time-point. In summary, the expression of EpCAM and PCNA was increased in DEN-induced tumors and the expression of EpCAM and PCNA was altered by DEN treatment in cultured cells. This suggests that EpCAM expression may be modulated in the progeny of adult liver stem cells during their differentiation toward hepatocytes and may be increased during DEN-induced hepatocarcinogenesis.

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