Modulation of iron-regulatory genes in human hepatocellular carcinoma and its physiological consequences

Experimental Biology and Medicine

Volumn 234, Issue 6, 2009, Pages 693-702

  Tan, Michelle Guet Khim ^a   Kumarasinghe, Marian Priyanthi ^b   Suk, Mei Wang ^c   Ooi, London Lucien P J ^a   Swee, Eng Aw ^a   Hui, Kam M ^c  

^a SINGAPORE GENERAL HOSPITAL   (Singapore)

^b UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^c DIVISION OF MEDICAL ONCOLOGY   (Singapore)

Author keywords

Hepatic iron deposition; Hepatocellular carcinoma; Hepcidin; Iron homeostasis; Iron regulatory genes

Indexed keywords

CERULOPLASMIN; HEPCIDIN; IRON REGULATORY FACTOR; IRON REGULATORY PROTEIN 1; TRANSFERRIN; TRANSFERRIN RECEPTOR 2;

ADULT; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; DOWN REGULATION; FEMALE; GENE EXPRESSION PROFILING; HEPATITIS B; HISTOLOGY; HOMEOSTASIS; HUMAN; HUMAN TISSUE; LIVER CELL CARCINOMA; MALE; MODULATION;

ADULT; CARCINOMA, HEPATOCELLULAR; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; HEPATITIS B, CHRONIC; HEPATITIS C, CHRONIC; HUMANS; IRON; LIVER NEOPLASMS; MALE; MIDDLE AGED; NEOPLASM PROTEINS; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS;

HEPATITIS B VIRUS;

EID: 66449089491     PISSN: 15353702     EISSN: 15353699     Source Type: Journal    
DOI: 10.3181/0807-RM-227     Document Type: Article

References (36)

1. Meneghini R. Iron homeostasis, oxidative stress, and DNA damage. Free Radic Biol Med 23:783-792, 1997. (Pubitemid 27364873)
2. Le NT, Richardson DR. The role of iron in cell cycle progression and the proliferation of neoplastic cells. Biochim Biophys Acta 1603:31-46, 2002. (Pubitemid 35257983)
3. Morgan EH. Iron metabolism and transport. In: Zakim D, Boyer TD, Eds. Hepatology: A textbook of liver disease. Philadelphia: W.B. Saunders Company, pp526-554, 1996.
4. Fleming RE, Bacon BR. Orchestration of iron homeostasis. N Engl J Med 352:1741-1744, 2005. (Pubitemid 40570920)
5. Nicolas G, Bennoun M, Devaux I, Beaumont C, Grandchamp B, Kahn A, Vaulont S. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci U S A 98:8780-8785, 2001. (Pubitemid 32678104)
6. Nicolas G, Bennoun M, Porteu A, Mativet S, Beaumont C, Grandchamp B, Sirito M, Sawadogo M, Kahn A, Vaulont S. Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc Natl Acad Sci U S A 99:4596-4601, 2002. (Pubitemid 34286030)
7. Roetto A, Papanikolaou G, Politou M, Alberti F, Girelli D, Christakis J, Loukopoulos D, Camaschella C. Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat Genet 33:21-22, 2003. (Pubitemid 36068676)
8. Bridle KR, Frazer DM, Wilkins SJ, Dixon JL, Purdie DM, Crawford DH, Subramaniam VN, Powell LW, Anderson GJ, Ramm GA. Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis. Lancet 361:669-673, 2003. (Pubitemid 36246550)
9. Piperno A, Girelli D, Nemeth E, Trombini P, Bozzini C, Poggiali E, Phung Y, Ganz T, Camaschella C. Blunted hepcidin response to oral iron challenge in HFE-related hemochromatosis. Blood 110:4096-4100, 2007. (Pubitemid 350248467)
10. Atanasiu V, Manolescu B, Stoian I. Hepcidin - central regulator of iron metabolism. Eur J Haematol 78:1-10, 2007. (Pubitemid 46018552)
11. Bradbear RA, Bain C, Siskind V, Schofield FD, Webb S, Axelsen EM, Halliday JW, Bassett ML, Powell LW. Cohort study of internal malignancy in genetic hemochromatosis and other chronic nonalcoholic liver diseases. J Natl Cancer Inst 75:81-84, 1985. (Pubitemid 15005959)
12. Asare GA, Mossanda KS, Kew MC, Paterson AC, Kahler-Venter CP, Siziba K. Hepatocellular carcinoma caused by iron overload: a possible mechanism of direct hepatocarcinogenicity. Toxicology 219:41-52, 2006. (Pubitemid 43120705)
13. Turlin B, Juguet F, Moirand R, Le Quilleuc D, Loreal O, Campion JP, Launois B, Ramee MP, Brissot P, Deugnier Y. Increased liver iron stores in patients with hepatocellular carcinoma developed on a noncirrhotic liver. Hepatology 22:446-450, 1995.
14. Chapoutot C, Esslimani M, Joomaye Z, Ramos J, Perney P, Laurent C, Fabbro-Peray P, Larrey D, Domergue J, Blanc F. Liver iron excess in patients with hepatocellular carcinoma developed on viral C cirrhosis. Gut 46:711-714, 2000. (Pubitemid 30305791)
15. Deugnier YM, Charalambous P, Le Quilleuc D, Turlin B, Searle J, Brissot P, Powell LW, Halliday JW. Preneoplastic significance of hepatic iron-free foci in genetic hemochromatosis: a study of 185 patients. Hepatology 18:1363-1369, 1993. (Pubitemid 23348423)
16. Williams GM, Klaiber M, Parker SE, Farber E. Nature of early appearing, carcinogen-induced liver lesions to iron accumulation. J Natl Cancer Inst 57:157-165, 1976.
17. Wang SM, Ooi LL, Hui KM. Identification and validation of a novel gene signature associated with the recurrence of human hepatocellular carcinoma. Clin Cancer Res 13:6275-6283, 2007. (Pubitemid 350075015)
18. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RN, et al. Histological grading and staging of chronic hepatitis. J Hepatol 22:696-699, 1995.
19. Searle JW, Leggett BA, Crawford DHG, Powell LW. Iron storage disease. In: MacSween RNM, Burt AD, Portmann BC, Ishak KG, Scheuer PJ, Anthony PP, Eds. Pathology of the Liver. Edinburgh: Churchill Livingstone, pp260, 2002.
20. Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 45:529-538, 2006. (Pubitemid 44307383)
21. Otegbayo JA, Arinola OG, Aje A, Oluwasola OA, Okiwelu OH, Salimonu LS. Usefulness of acute phase proteins for monitoring development of hepatocellular carcinoma in hepatitis B virus carriers. West Afr J Med 24:124-127, 2005. (Pubitemid 41057367)
22. Martinelli AL, Filho AB, Franco RF, Tavella MH, Ramalho LN, Zucoloto S, Rodrigues SS, Zago MA. Liver iron deposits in hepatitis B patients: association with severity of liver disease but not with hemochromatosis gene mutations. J Gastroenterol Hepatol 19:1036-1041, 2004. (Pubitemid 39237439)
23. Batts KP. Iron overload syndromes and the liver. Mod Pathol 20 Suppl 1:S31-S39, 2007. (Pubitemid 46733661)
24. Fujita N, Sugimoto R, Ma N, Tanaka H, Iwasa M, Kobayashi Y, Kawanishi S, Watanabe S, Kaito M, Takei Y. Comparison of hepatic oxidative DNA damage in patients with chronic hepatitis B and C. J Viral Hepat 15:498-507, 2008.
25. Hentze MW, Muckenthaler MU, Andrews NC. Balancing acts: molecular control of mammalian iron metabolism. Cell 117:285-297, 2004. (Pubitemid 38534536)
26. Camaschella C. Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders. Blood 106:3710-3717, 2005. (Pubitemid 41739004)
27. Park KS, Kim H, Kim NG, Cho SY, Choi KH, Seong JK, Paik YK. Proteomic analysis and molecular characterization of tissue ferritin light chain in hepatocellular carcinoma. Hepatology 35:1459-1466, 2002. (Pubitemid 34966900)
28. West AP Jr, Bennett MJ, Sellers VM, Andrews NC, Enns CA, Bjorkman PJ. Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE. J Biol Chem 275:38135-38138, 2000. (Pubitemid 32009130)
29. Holmström P, Gåfvels M, Eriksson LC, Dzikaite V, Hultcrantz R, Eggertsen G, Stål P. Expression of iron regulatory genes in a rat model of hepatocellular carcinoma. Liver Int 26:976, 2006. (Pubitemid 44323416)
30. Kijima H, Sawada T, Tomosugi N, Kubota K. Expression of hepcidin mRNA is uniformly suppressed in hepatocellular carcinoma. BMC Cancer 8:167, 2008.
31. Aoki CA, Rossaro L, Ramsamooj R, Brandhagen D, Burritt MF, Bowlus CL. Liver hepcidin mRNA correlates with iron stores, but not inflammation, in patients with chronic hepatitis C. J Clin Gastroenterol 39:71-74, 2005. (Pubitemid 40041349)
32. Takeo M, Kobayashi Y, Fujita N, Urawa N, Iwasa M, Horiike S, Tanaka H, Kaito M, Adachi Y. Upregulation of transferrin receptor 2 and ferroportin 1 mRNA in the liver of patients with chronic hepatitis C. J Gastroenterol Hepatol 20:562-569, 2005. (Pubitemid 40755268)
33. Theurl I, Ludwiczek S, Eller P, Seifert M, Artner E, Brunner P, Weiss G. Pathways for the regulation of body iron homeostasis in response to experimental iron overload. J Hepatol 43:711-719, 2005. (Pubitemid 41253240)
34. Kawabata H, Fleming RE, Gui D, Moon SY, Saitoh T, O'Kelly J, Umehara Y, Wano Y, Said JW, Koeffler HP. Expression of hepcidin is down-regulated in TfR2 mutant mice manifesting a phenotype of hereditary hemochromatosis. Blood 105:376-381, 2005. (Pubitemid 40053107)
35. Muckenthaler MU, Rodrigues P, Macedo MG, Minana B, Brennan K, Cardoso EM, Hentze MW, de Sousa M. Molecular analysis of iron overload in beta2-microglobulin-deficient mice. Blood Cells Mol Dis 33:125-131, 2004. (Pubitemid 39099293)
36. Nemeth E, Roetto A, Garozzo G, Ganz T, Camaschella C. Hepcidin is decreased in TFR2 hemochromatosis. Blood 105:1803-1806, 2005.