Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
권호 표지

Alteration of X-linked Inhibitors of Apoptosis (XIAP) Expression in Rat Model with DEN-induced Hepatocellular Carcinogenesis

  • Chang, Jae-Jin (Orient Bio Inc.) ;
  • Jeon, Su-Yeon (Graduate School of Life Science and Biotechonology, College of Medicine, Pochon CHA University) ;
  • Song, Ji-Ye (Graduate School of Life Science and Biotechonology, College of Medicine, Pochon CHA University) ;
  • Kim, Jin-Hee (Graduate School of Life Science and Biotechonology, College of Medicine, Pochon CHA University) ;
  • Li, Lan (College of Veterinary Medicine, Kangwon National University) ;
  • Park, Dae-Hun (Development of Herbal Pharmaceutical Development, Korea Institute of Oriental Medicine) ;
  • Lee, Yun-Lyul (Department of Physilolgy, College of Medicine, Hallym University) ;
  • Park, Jeong-Joo (College of Veterinary Medicine, Kangwon National University) ;
  • Woo, Dong-Wook (College of Veterinary Medicine, Kangwon National University) ;
  • Kim, Gi-Jin (Graduate School of Life Science and Biotechonology, College of Medicine, Pochon CHA University) ;
  • Lee, Min-Jae (College of Veterinary Medicine, Kangwon National University)
  • Published : 2008.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

The X-linked inhibitor of apoptosis (XIAP) is a member of a novel family of inhibitors of apoptosis and has several BIR domains (BIR1, BIR2, and BIR3) and a carboxy-terminal RING zinc-finger. Since suppressionof apoptosis is fundamentally important for carcinogenesis and tumor growth, we investigated the expression and function of XIAP in DEN-induced carcinogenesis using rat model. Wistar rats were injected intraperitoneally with DEN at a dose of 50 mg/kg in twice a week for 12 weeks (Group II) and 16 weeks (Group III) followed by the recovery periods, respectively. The evaluation of DEN-induced carcinogenesis carried out the blood, RT-PCR, histopathological and western blot analysis. The level of blood chemistry including GOT/GPT, albumin, and total bilirubin were significantly exchanged comparing to control and Group I/Group II. The expression of albumin and collagen mRNA were significantly exchanged (P<0.05) in both groups. In addition, AFP mRNA expression decreased more after recovery periods than Group II. XIAP was expressed constitutively in normal rat liver as well as DEN-induced Groups I and Group II. In addition, XIAP expression increased more in Group I with 4 weeks recovery periods than Group I. However, XIAP expression shown to increase in Group lI, otherwise, it was decreased in Group II with 10 weeks repair periods. Taken together, these results suggest the alteration of XIAP expression could be involved in hepatocellular carcinogenesis.

Keywords

References

  1. Yagumr, E., Rizk, M. & Stanzel, S. Elevation of endoglin (CD105) concentrations in serum of patients with liver cirrhosis and carcinoma. Eur J Gastroenterol & Hepatol 19:755-761 (2007) https://doi.org/10.1097/MEG.0b013e3282202bea
  2. Rasi, G., Serafino, N. & Bellis, L. Nerve growth factor involvement in liver cirrhosis and hepatocellular carcinoma. World J Gastroenterol 13:4986-4995 (2007) https://doi.org/10.3748/wjg.v13.i37.4986
  3. Hertl, M. & Cosimi, A. B. Liver transplantation for malignancy. The Oncologist 10:269-281 (2005) https://doi.org/10.1634/theoncologist.10-4-269
  4. Coleman, W. B. Mechanisms of human hepatocarcinogenesis. Curr Mol Med 6:573-588 (2003)
  5. Caja, L., Ortiz, C. & Bertran, E. Differential intracellular signaling induced by TGF-${\beta}$ in rat adult hepatocytes and hepatoma cells: Implications in liver carcinogenesis. Cell Signal 19:683-694 (2007) https://doi.org/10.1016/j.cellsig.2006.09.002
  6. Fabregat, I., Roncero, C. & Fernádez, M. Survival and apoptosis:a dysregulated balance in liver cancer. Liver Int 2:155-162 (2007)
  7. Ellis, M. C., Yuan, J. Y. & Horvitz, H. R. Mechanisms and function of cell death. ANnu Rev Cell Biol 7:663-698 (1991) https://doi.org/10.1146/annurev.cb.07.110191.003311
  8. Stellaer, H. Mechanisms and genes of cellular suicide. Science 267:1445-1449 (1995) https://doi.org/10.1126/science.7878463
  9. Thompson, J., Finlayson, K. & Salvo-Chirnside, E. Characterization of the Bax-nucleophosmin interaction: the importance of the bax C-terminus. Apoptosis 13:394-403 (2008) https://doi.org/10.1007/s10495-007-0177-2
  10. Li, J. et al. Human ovarian cancer and cisplatin resistance: possible role of inhibitor of apoptosis proteins. Endocrinology 142:370-380 (2001) https://doi.org/10.1210/en.142.1.370
  11. Crook, N. E., Clem, R. J. & Miller, L. K. An apoptosis-inhibiting baculovirus gene with a zing finger-like motif. J Virol 67:2168-2174 (1993)
  12. Liston, P., Roy, N. & Tamai, K. Suppression of apoptosis in mammalian cells by Naip and a related family. Nature 379:349-353 (1996) https://doi.org/10.1038/379349a0
  13. Duckett, C. S., Nava, V. E. & Gedrich, R. W. A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors. EMBO J 15:2685-2694 (1996)
  14. Deveraux, Q. L., Takahashi, R. & Salvesen, G. S. X-linked IAP is a direct inhibitor of cell-death proteases. Nature 388:300-304 (1997) https://doi.org/10.1038/40901
  15. Holick, M., Gibson, H. & Korneluk, R. G. Apoptotic brake and promising therapeutic target. Apopsis 6:253-261 (2001)
  16. Sakemi, R., Yano, H. & Ogasawara, S. X-linked inhibitor of apoptosis (XIAP) and XIAP-associated factor-1 expressions and their relationship to apoptosis in human hepatocellular carcinoma and non-cancerous liver tissues. Oncol Rep 18:65-70 (2007)
  17. Liston, P., Fong, W. G. & Kelly, N. L. Identification of XAF1 as an antagonist of XIAP anti-Caspase activity. Nature Cell Biology 3:128-133 (2001) https://doi.org/10.1038/35055027
  18. Fong, W. G., Liston, P. & Rajcan-Separovic, E. Expression and genetic analysis of XIAP-associated factor 1 (XAF1) in cancer cell lines. Genomics 70:113-122 (2000) https://doi.org/10.1006/geno.2000.6364
  19. Seligson, D. B., Hongo, F. & Huerta-Yepez, S. Expression of X-linked inhibitor of apoptosis protein is a strong predictor of human prostate cancer recurrence. Clin Cancer Res 13:6056-6063 (2007) https://doi.org/10.1158/1078-0432.CCR-07-0960
  20. Shiraki, K., Sugimoto, K. & Yamanaka, Y. Overexpression of X-linked inhibitor of apoptosis n human hepatocelluar carcinoma. Int J Mol Med 12:705-708 (2003)
  21. Lijinsky, W., Kovatch, R. M. & Riggs, C. W. Doseresponse study with N-nitrosomorpholine in drinking water of F-344 rats. Cancer Res 48:2089-2095 (1988)
  22. Volm, M., Zerban, H. & Mattern, J. Overexpression of P-glycoprotein in rat hepatocellular carcinomas induced with N-nitrosomorphline. Carcinogenesis 11:169-172 (1990) https://doi.org/10.1093/carcin/11.1.169
  23. Weber, E. & Bannasch, P. Dose and time dependence of the cellular phenotype in rat hepatic preneoplasia and neoplasia induced by continuous oral exposure to N-nitrosomorpline. Carcinogenesis 15:1235-1242 (1994) https://doi.org/10.1093/carcin/15.6.1235
  24. Enzmann, H., Zerban, H. & Kopp, S. A. Effects of low doses of N-nitrosomorpholine on the development of early stages of hepatocarcinogenesis. Carcinogenesis 16:1513-1518 (1995) https://doi.org/10.1093/carcin/16.7.1513
  25. Schere, E. & Emmelot, P. Kinetics of induction and growth of precancerous liver-cell foci, ad liver tumor formation by diethylnitrosamine in the rat. Eur J Cancer 11:689-696 (1975) https://doi.org/10.1016/0014-2964(75)90042-0
  26. Chen, P. J. & Chen, D. S. Hepatitis B virus infection and hepatocellular carcinoma: molecular genetics and clinical perspectives. Semin Liver Dis 19: 253-262 (1999) https://doi.org/10.1055/s-2007-1007115
  27. Masaki, T., Shiratori, Y. & Rengifo, W. Hepatocellular carcinoma cell cycle: study of Long-Evans cinnamon rats. Hepatology 32:711-720 (2000) https://doi.org/10.1053/jhep.2000.17705
  28. Matsuda, Y., Ichida, T. & Genda, T. Loss of p16 contributes to p27 sequestration by cyclin D(1)-cyclindependent kinase 4 complexes and poor prognosis in hepatocellular carcinoma. Clin Cancer Res 15:3389-3396 (2003)
  29. Higaki, S., Akazawa, A. & Nakamura, H. Metaplastic polyp of the colon develops in response to inflammation. J Gastroenterol Hepatol 14:709-714 (1999) https://doi.org/10.1046/j.1440-1746.1999.01938.x
  30. Nardone, G., Staibano, S. & Rocco, A. Effect of helicobacter pylori infection and its eradication on cell proliferation, DNA safety, and oncogene expression in patients with chronic gastritis. Gut 44:789-799 (1999) https://doi.org/10.1136/gut.44.6.789
  31. Tsunematsu, S., Satio, H. & Tada, S. Susceptibility of experimental autoimmune hepatitis in transgenic mice overexpressing the C-H-ras gene. J Gastroenterol Hepatol 4:319-324 (1997)
  32. Kojiro, M. X-linked inhibitor of apoptosis (XIAP) and XIAP-associated factor-1 expressions and their relationship to apoptosis in human hepatocellular carcinoma and non-cancerous liver tissues. Oncol Rep 18:65-70 (2007)
  33. Seligson, D. B., Hongo, F. & Huerta-Yepez, S. Expression of X-linked inhibitor of apoptosis protein is a strong predictor of human prostate cancer recurrence. Clin Cancer Res 13:6056-6063 (2007) https://doi.org/10.1158/1078-0432.CCR-07-0960