DOI QR코드

DOI QR Code

Increased Expression of Epithelial Cell Adhesion Molecule (EpCAM) in Rat Hepatic Tumors Induced by Diethylnitrosamine

  • Kang, Jin Seok (Department of Biomedical Laboratory Science, Namseoul University)
  • Published : 2012.08.31

Abstract

The epithelial cell adhesion molecule (EpCAM) is a pan-epithelial differentiation antigen that is expressed on almost all carcinomas. However, a role in rat liver carcinogenesis has never been reported previously. Thus, its expression was investigated herein in rat liver tumors induced by diethylnitrosamine (DEN). Twenty male 5-week-old F344 rats were used in this experiment. Mini-osmotic pumps containing doses of 47.5 mg of DEN were inserted into the abdominal cavity of each animal to initiate liver carcinogenesis. All animals were sacrificed at 26 weeks after DEN treatment. At necropsy, hepatic masses were processed for histopathological examination, which revealed forty-four hepatocellular adenomas (HCAs) and twenty hepatocellular carcinomas (HCC). Tumors were immunohistochemically analyzed for EpCAM, proliferating cell nuclear antigen (PCNA) and co-localization of the two. EpCAM expression was mainly detected in hepatic tumor cells, showing a cytoplasmic staining pattern. However, expression was also slightly observed in normally-appearing surrounding hepatic cells. PCNA expression was highly detected in tumor cells, showing nuclear staining. Double staining of EpCAM and PCNA in tumors showed many cells with co-localization. Taken together, EpCAM and PCNA expression were increased in DEN-induced tumors and many tumor cells showed co-expression. It is suggested that EpCAM may increase during DEN-induced tumors, possibly associated with cell proliferation.

Keywords

Hepatocarcinogenesis;DEN;EpCAM;PCNA;rat

References

  1. Al-Hajj M, Clarke MF (2004). Self-renewal and solid tumor stem cells. Oncogene, 23, 7274-82. https://doi.org/10.1038/sj.onc.1207947
  2. Arsura M and Cavin LG (2005). Nuclear factor-kappaB and liver carcinogenesis. Cancer Lett, 229, 157-69. https://doi.org/10.1016/j.canlet.2005.07.008
  3. Kang JS, Wanibuchi H, Morimura K, et al (2007). Role of CYP2E1 in diethylnitrosamine-induced hepatocarcinogenesis in vivo. Cancer Res, 67, 11141-6. https://doi.org/10.1158/0008-5472.CAN-07-1369
  4. Kenyon J, Gerson SL (2007). The role of DNA damage repair in aging of adult stem cells. Nucleic Acids Res, 35, 7557-65. https://doi.org/10.1093/nar/gkm1064
  5. Litvinov SV, Velders MP, Bakker HA, et al (1994). Ep-CAM: a human epithelial antigen is a homophilic cell-cell adhesion molecule. J Cell Biol, 125, 437-46. https://doi.org/10.1083/jcb.125.2.437
  6. Maetzel D, Denzel S, Mack B, et al (2009). Nuclear signalling by tumour-associated antigen EpCAM. Nat Cell Biol, 11, 162-71. https://doi.org/10.1038/ncb1824
  7. Peto R, Gray R, Brantom P, et al (1991). Effects on 4080 rats of chronic ingestion of N-nitrosodiethylamine or N-nitrosodimethylamine: a detailed dose-response study. Cancer Res, 51, 6415-51.
  8. Pitot HC, Dragan YP, Teeguarden J, et al (1996). Quantitation of multistage carcinogenesis in rat liver. Toxicol Pathol, 24, 119-128. https://doi.org/10.1177/019262339602400116
  9. Sell S and Dunsford HA (1989). Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma. Am J Pathol, 134, 1347-63.
  10. Turner R, Lozoya O, Wang Y, et al (2011). Human hepatic stem cell and maturational liver lineage biology. Hepatology, 53, 1035-45. https://doi.org/10.1002/hep.24157
  11. van der Gun BT, Melchers LJ, Ruiters MH, et al (2010). EpCAM in carcinogenesis: the good, the bad or the ugly. Carcinogenesis, 31, 1913-21. https://doi.org/10.1093/carcin/bgq187
  12. Verna L, Whysner J, Williams GM (1996). N-nitrosodiethylamine mechanistic data and risk assessment: bioactivation, DNA-adduct formation, mutagenicity, and tumor initiation. Pharmacol Ther, 71, 57-81. https://doi.org/10.1016/0163-7258(96)00062-9
  13. Visvader JE, Lindeman GJ (2008). Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer, 8, 755-68. https://doi.org/10.1038/nrc2499
  14. Wicha MS, Liu S, Dontu G (2006). Cancer stem cells: an old idea--a paradigm shift. Cancer Res, 66, 1883-1890; discussion 1895-86. https://doi.org/10.1158/0008-5472.CAN-05-3153
  15. Yamashita T, Forgues M, Wang W, et al (2008). EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res, 68, 1451-61. https://doi.org/10.1158/0008-5472.CAN-07-6013
  16. Yamashita T, Ji J, Budhu A, et al (2009). EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology, 136, 1012-24. https://doi.org/10.1053/j.gastro.2008.12.004
  17. Yoon SM, Gerasimidou D, Kuwahara R, et al (2011). Epithelial cell adhesion molecule (EpCAM) marks hepatocytes newly derived from stem/progenitor cells in humans. Hepatology, 53, 964-73. https://doi.org/10.1002/hep.24122

Cited by

  1. Preventive Effect of Hydrazinocurcumin on Carcinogenesis of Diethylnitrosamine-induced Hepatocarcinoma in Male SD Rats vol.15, pp.5, 2014, https://doi.org/10.7314/APJCP.2014.15.5.2115