
Human hepatocyte carcinogenesis (Review)
- Authors:
- Hidenori Shiraha
- Kazuhide Yamamoto
- Masayoshi Namba
-
Affiliations: Department of Gastroenterology and Hepatology, Okayama University Faculty of Medicine, Okayama 700-8558, Japan, Niimi College, Nishikata 1263-2, Niimi 718-8585, Japan - Published online on: February 19, 2013 https://doi.org/10.3892/ijo.2013.1829
- Pages: 1133-1138
-
Copyright: © Shiraha et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
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El-Serag HB and Rudolph KL: Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 132:2557–2576. 2007. View Article : Google Scholar : PubMed/NCBI | |
Garcia M, Jernal A, Ward EM, et al: Global Cancer Facts & Figures 2007. Journal. 2007. | |
Parkin DM, Pisani P and Ferlay J: Global cancer statistics. CA Cancer J Clin. 49:33–64. 1999. View Article : Google Scholar | |
Bosch FX, Ribes J and Borras J: Epidemiology of primary liver cancer. Semin Liver Dis. 19:271–285. 1999. View Article : Google Scholar : PubMed/NCBI | |
El-Serag HB and Mason AC: Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med. 340:745–750. 1999. View Article : Google Scholar : PubMed/NCBI | |
Nakakura EK and Choti MA: Management of hepatocellular carcinoma. Oncology (Williston Park). 14:1085–1102. 2000. | |
El-Serag HB, Marrero JA, Rudolph L and Reddy KR: Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology. 134:1752–1763. 2008. View Article : Google Scholar : PubMed/NCBI | |
Llovet JM, Ricci S, Mazzaferro V, et al: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 359:378–390. 2008. View Article : Google Scholar : PubMed/NCBI | |
Nigro JM, Baker SJ, Preisinger AC, et al: Mutations in the p53 gene occur in diverse human tumour types. Nature. 342:705–708. 1989. View Article : Google Scholar : PubMed/NCBI | |
Levine AJ, Momand J and Finlay CA: The p53 tumour suppressor gene. Nature. 351:453–456. 1991. View Article : Google Scholar : PubMed/NCBI | |
Hollstein M, Sidransky D, Vogelstein B and Harris CC: p53 mutations in human cancers. Science. 253:49–53. 1991. View Article : Google Scholar : PubMed/NCBI | |
Bressac B, Galvin KM, Liang TJ, Isselbacher KJ, Wands JR and Ozturk M: Abnormal structure and expression of p53 gene in human hepatocellular carcinoma. Proc Natl Acad Sci USA. 87:1973–1977. 1990. View Article : Google Scholar : PubMed/NCBI | |
Bourdon JC: p53 and its isoforms in cancer. Br J Cancer. 97:277–282. 2007. View Article : Google Scholar : PubMed/NCBI | |
Vousden KH and Lane DP: p53 in health and disease. Nat Rev Mol Cell Biol. 8:275–283. 2007. View Article : Google Scholar | |
Ozturk M: Genetic aspects of hepatocellular carcinogenesis. Semin Liver Dis. 19:235–242. 1999. View Article : Google Scholar | |
Tannapfel A, Busse C, Weinans L, et al: INK4a-ARF alterations and p53 mutations in hepatocellular carcinomas. Oncogene. 20:7104–7109. 2001. View Article : Google Scholar : PubMed/NCBI | |
Bressac B, Kew M, Wands J and Ozturk M: Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa. Nature. 350:429–431. 1991. View Article : Google Scholar : PubMed/NCBI | |
Buendia MA: Genetics of hepatocellular carcinoma. Semin Cancer Biol. 10:185–200. 2000. View Article : Google Scholar | |
Teramoto T, Satonaka K, Kitazawa S, Fujimori T, Hayashi K and Maeda S: p53 gene abnormalities are closely related to hepatoviral infections and occur at a late stage of hepatocarcinogenesis. Cancer Res. 54:231–235. 1994.PubMed/NCBI | |
Ueda H, Ullrich SJ, Gangemi JD, et al: Functional inactivation but not structural mutation of p53 causes liver cancer. Nat Genet. 9:41–47. 1995. View Article : Google Scholar : PubMed/NCBI | |
Pantoja E, Beecher TS and Cross VF: Cutaneous lymphangiosarcoma of Stewart-Treves. Cutis. 17:883–886. 1976.PubMed/NCBI | |
Hanahan D and Weinberg RA: The hallmarks of cancer. Cell. 100:57–70. 2000. View Article : Google Scholar | |
Higashitsuji H, Itoh K, Nagao T, et al: Reduced stability of retinoblastoma protein by gankyrin, an oncogenic ankyrin-repeat protein overexpressed in hepatomas. Nat Med. 6:96–99. 2000. View Article : Google Scholar : PubMed/NCBI | |
Hsia CC, Di Bisceglie AM, Kleiner DE Jr, Farshid M and Tabor E: RB tumor suppressor gene expression in hepatocellular carcinomas from patients infected with the hepatitis B virus. J Med Virol. 44:67–73. 1994. View Article : Google Scholar : PubMed/NCBI | |
Azechi H, Nishida N, Fukuda Y, et al: Disruption of the p16/ cyclin D1/retinoblastoma protein pathway in the majority of human hepatocellular carcinomas. Oncology. 60:346–354. 2001. View Article : Google Scholar : PubMed/NCBI | |
Liew CT, Li HM, Lo KW, et al: High frequency of p16INK4A gene alterations in hepatocellular carcinoma. Oncogene. 18:789–795. 1999. View Article : Google Scholar : PubMed/NCBI | |
Matsuda Y, Ichida T, Matsuzawa J, Sugimura K and Asakura H: p16(INK4) is inactivated by extensive CpG methylation in human hepatocellular carcinoma. Gastroenterology. 116:394–400. 1999. View Article : Google Scholar : PubMed/NCBI | |
Li DM and Sun H: PTEN/MMAC1/TEP1 suppresses the tumorigenicity and induces G1 cell cycle arrest in human glioblastoma cells. Proc Natl Acad Sci USA. 95:15406–15411. 1998. View Article : Google Scholar : PubMed/NCBI | |
Hu TH, Huang CC, Lin PR, et al: Expression and prognostic role of tumor suppressor gene PTEN/MMAC1/TEP1 in hepatocellular carcinoma. Cancer. 97:1929–1940. 2003. View Article : Google Scholar : PubMed/NCBI | |
Li QL, Ito K, Sakakura C, et al: Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell. 109:113–124. 2002. View Article : Google Scholar : PubMed/NCBI | |
Mori T, Nomoto S, Koshikawa K, et al: Decreased expression and frequent allelic inactivation of the RUNX3 gene at 1p36 in human hepatocellular carcinoma. Liver Int. 25:380–388. 2005. View Article : Google Scholar : PubMed/NCBI | |
Miyagawa K, Sakakura C, Nakashima S, et al: Down-regulation of RUNX1, RUNX3 and CBFbeta in hepatocellular carcinomas in an early stage of hepatocarcinogenesis. Anticancer Res. 26:3633–3643. 2006.PubMed/NCBI | |
Li X, Zhang Y, Qiao T, et al: RUNX3 inhibits growth of HCC cells and HCC xenografts in mice in combination with adriamycin. Cancer Biol Ther. 7:669–676. 2008. View Article : Google Scholar : PubMed/NCBI | |
Nakanishi Y, Shiraha H, Nishina S, et al: Loss of runt-related transcription factor 3 expression leads hepatocellular carcinoma cells to escape apoptosis. BMC Cancer. 11:32011. View Article : Google Scholar : PubMed/NCBI | |
Tanaka S, Shiraha H, Nakanishi Y, et al: Runt-related transcription factor 3 reverses epithelial-mesenchymal transition in hepato-cellular carcinoma. Int J Cancer. 131:2537–2546. 2012. View Article : Google Scholar | |
Fujimoto Y, Hampton LL, Wirth PJ, Wang NJ, Xie JP and Thorgeirsson SS: Alterations of tumor suppressor genes and allelic losses in human hepatocellular carcinomas in China. Cancer Res. 54:281–285. 1994. | |
Kawai H, Suda T, Aoyagi Y, et al: Quantitative evaluation of genomic instability as a possible predictor for development of hepatocellular carcinoma: comparison of loss of heterozygosity and replication error. Hepatology. 31:1246–1250. 2000. View Article : Google Scholar | |
Nishida N, Nagasaka T, Nishimura T, Ikai I, Boland CR and Goel A: Aberrant methylation of multiple tumor suppressor genes in aging liver, chronic hepatitis, and hepatocellular carcinoma. Hepatology. 47:908–918. 2008. View Article : Google Scholar | |
Yang B, Guo M, Herman JG and Clark DP: Aberrant promoter methylation profiles of tumor suppressor genes in hepatocellular carcinoma. Am J Pathol. 163:1101–1107. 2003. View Article : Google Scholar : PubMed/NCBI | |
Wang Y, Wu MC, Sham JS, Zhang W, Wu WQ and Guan XY: Prognostic significance of c-myc and AIB1 amplification in hepatocellular carcinoma. A broad survey using high-throughput tissue microarray. Cancer. 95:2346–2352. 2002. View Article : Google Scholar : PubMed/NCBI | |
Shachaf CM, Kopelman AM, Arvanitis C, et al: MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature. 431:1112–1117. 2004. View Article : Google Scholar : PubMed/NCBI | |
Tada M, Omata M and Ohto M: Analysis of ras gene mutations in human hepatic malignant tumors by polymerase chain reaction and direct sequencing. Cancer Res. 50:1121–1124. 1990.PubMed/NCBI | |
Challen C, Guo K, Collier JD, Cavanagh D and Bassendine MF: Infrequent point mutations in codons 12 and 61 of ras oncogenes in human hepatocellular carcinomas. J Hepatol. 14:342–346. 1992. View Article : Google Scholar : PubMed/NCBI | |
Stork P, Loda M, Bosari S, Wiley B, Poppenhusen K and Wolfe H: Detection of K-ras mutations in pancreatic and hepatic neoplasms by non-isotopic mismatched polymerase chain reaction. Oncogene. 6:857–862. 1991.PubMed/NCBI | |
Weihrauch M, Benick M, Lehner G, et al: High prevalence of K-ras-2 mutations in hepatocellular carcinomas in workers exposed to vinyl chloride. Int Arch Occup Environ Health. 74:405–410. 2001. View Article : Google Scholar : PubMed/NCBI | |
Davies H, Bignell GR, Cox C, et al: Mutations of the BRAF gene in human cancer. Nature. 417:949–954. 2002. View Article : Google Scholar : PubMed/NCBI | |
de La Coste A, Romagnolo B, Billuart P, et al: Somatic mutations of the beta-catenin gene are frequent in mouse and human hepatocellular carcinomas. Proc Natl Acad Sci USA. 95:8847–8851. 1998.PubMed/NCBI | |
Csepregi A, Rocken C, Hoffmann J, et al: APC promoter methylation and protein expression in hepatocellular carcinoma. J Cancer Res Clin Oncol. 134:579–589. 2008. View Article : Google Scholar : PubMed/NCBI | |
Legoix P, Bluteau O, Bayer J, et al: Beta-catenin mutations in hepatocellular carcinoma correlate with a low rate of loss of heterozygosity. Oncogene. 18:4044–4046. 1999. View Article : Google Scholar : PubMed/NCBI | |
Huang S, He J, Zhang X, et al: Activation of the hedgehog pathway in human hepatocellular carcinomas. Carcinogenesis. 27:1334–1340. 2006. View Article : Google Scholar : PubMed/NCBI | |
Nusslein-Volhard C and Wieschaus E: Mutations affecting segment number and polarity in Drosophila. Nature. 287:795–801. 1980. View Article : Google Scholar : PubMed/NCBI | |
Nybakken K and Perrimon N: Hedgehog signal transduction: recent findings. Curr Opin Genet Dev. 12:503–511. 2002. View Article : Google Scholar : PubMed/NCBI | |
Cohen MM Jr and Shiota K: Teratogenesis of holoprosencephaly. Am J Med Genet. 109:1–15. 2002. View Article : Google Scholar : PubMed/NCBI | |
Mullor JL, Sanchez P and Ruiz i Altaba A: Pathways and consequences: Hedgehog signaling in human disease. Trends Cell Biol. 12:562–569. 2002. View Article : Google Scholar : PubMed/NCBI | |
Stecca B, Mas C and Ruiz i Altaba A: Interference with HH-GLI signaling inhibits prostate cancer. Trends Mol Med. 11:199–203. 2005. View Article : Google Scholar : PubMed/NCBI | |
Patil MA, Zhang J, Ho C, Cheung ST, Fan ST and Chen X: Hedgehog signaling in human hepatocellular carcinoma. Cancer Biol Ther. 5:111–117. 2006. View Article : Google Scholar : PubMed/NCBI | |
Schaff Z, Hsia CC, Sarosi I and Tabor E: Overexpression of transforming growth factor-alpha in hepatocellular carcinoma and focal nodular hyperplasia from European patients. Hum Pathol. 25:644–651. 1994. View Article : Google Scholar : PubMed/NCBI | |
Hsia CC, Axiotis CA, Di Bisceglie AM and Tabor E: Transforming growth factor-alpha in human hepatocellular carcinoma and coexpression with hepatitis B surface antigen in adjacent liver. Cancer. 70:1049–1056. 1992. View Article : Google Scholar : PubMed/NCBI | |
Yamada T, De Souza AT, Finkelstein S and Jirtle RL: Loss of the gene encoding mannose 6-phosphate/insulin-like growth factor II receptor is an early event in liver carcinogenesis. Proc Natl Acad Sci USA. 94:10351–10355. 1997. View Article : Google Scholar : PubMed/NCBI | |
De Souza AT, Hankins GR, Washington MK, Orton TC and Jirtle RL: M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity. Nat Genet. 11:447–449. 1995.PubMed/NCBI | |
Dennis PA and Rifkin DB: Cellular activation of latent transforming growth factor beta requires binding to the cation-independent mannose 6-phosphate/insulin-like growth factor type II receptor. Proc Natl Acad Sci USA. 88:580–584. 1991. View Article : Google Scholar | |
Kawate S, Takenoshita S, Ohwada S, et al: Mutation analysis of transforming growth factor beta type II receptor, Smad2, and Smad4 in hepatocellular carcinoma. Int J Oncol. 14:127–131. 1999.PubMed/NCBI | |
Harley CB: Telomere loss: mitotic clock or genetic time bomb? Mutat Res. 256:271–282. 1991. View Article : Google Scholar : PubMed/NCBI | |
Harley CB, Futcher AB and Greider CW: Telomeres shorten during ageing of human fibroblasts. Nature. 345:458–460. 1990. View Article : Google Scholar : PubMed/NCBI | |
Counter CM, Avilion AA, LeFeuvre CE, et al: Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J. 11:1921–1929. 1992.PubMed/NCBI | |
Kim NW, Piatyszek MA, Prowse KR, et al: Specific association of human telomerase activity with immortal cells and cancer. Science. 266:2011–2015. 1994. View Article : Google Scholar : PubMed/NCBI | |
Counter CM, Hirte HW, Bacchetti S and Harley CB: Telomerase activity in human ovarian carcinoma. Proc Natl Acad Sci USA. 91:2900–2904. 1994. View Article : Google Scholar : PubMed/NCBI | |
Hiyama E, Gollahon L, Kataoka T, et al: Telomerase activity in human breast tumors. J Natl Cancer Inst. 88:116–122. 1996. View Article : Google Scholar : PubMed/NCBI | |
Shay JW and Bacchetti S: A survey of telomerase activity in human cancer. Eur J Cancer. 33:787–791. 1997. View Article : Google Scholar : PubMed/NCBI | |
Kojima H, Yokosuka O, Imazeki F, Saisho H and Omata M: Telo merase activity and telomere length in hepatocellular carcinoma and chronic liver disease. Gastroenterology. 112:493–500. 1997. View Article : Google Scholar : PubMed/NCBI | |
Nagao K, Tomimatsu M, Endo H, Hisatomi H and Hikiji K: Telomerase reverse transcriptase mRNA expression and telomerase activity in hepatocellular carcinoma. J Gastroenterol. 34:83–87. 1999. View Article : Google Scholar : PubMed/NCBI | |
Namba M, Mihara K and Fushimi K: Immortalization of human cells and its mechanisms. Crit Rev Oncog. 7:19–31. 1996. View Article : Google Scholar : PubMed/NCBI | |
McCormick JJ and Maher VM: Towards an understanding of the malignant transformation of diploid human fibroblasts. Mutat Res. 199:273–291. 1988. View Article : Google Scholar : PubMed/NCBI | |
Linder S and Marshall H: Immortalization of primary cells by DNA tumor viruses. Exp Cell Res. 191:1–7. 1990. View Article : Google Scholar : PubMed/NCBI | |
Schippers IJ, Moshage H, Roelofsen H, et al: Immortalized human hepatocytes as a tool for the study of hepatocytic (de-)differentiation. Cell Biol Toxicol. 13:375–386. 1997. View Article : Google Scholar : PubMed/NCBI | |
Strickler HD, Rosenberg PS, Devesa SS, Hertel J, Fraumeni JF Jr and Goedert JJ: Contamination of poliovirus vaccines with simian virus 40 (1955–1963) and subsequent cancer rates. JAMA. 279:292–295. 1998. | |
Faller DV, Kourembanas S, Ginsberg D, et al: Immortalization of human endothelial cells by murine sarcoma viruses, without morphologic transformation. J Cell Physiol. 134:47–56. 1988. View Article : Google Scholar | |
Morgan TL, Yang DJ, Fry DG, et al: Characteristics of an infinite life span diploid human fibroblast cell strain and a near-diploid strain arising from a clone of cells expressing a transfected v-myc oncogene. Exp Cell Res. 197:125–136. 1991. View Article : Google Scholar : PubMed/NCBI | |
Moriya K, Nakagawa K, Santa T, et al: Oxidative stress in the absence of inflammation in a mouse model for hepatitis C virus-associated hepatocarcinogenesis. Cancer Res. 61:4365–4370. 2001.PubMed/NCBI | |
Ray RB, Meyer K and Ray R: Hepatitis C virus core protein promotes immortalization of primary human hepatocytes. Virology. 271:197–204. 2000. View Article : Google Scholar : PubMed/NCBI | |
Moriya K, Fujie H, Shintani Y, et al: The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat Med. 4:1065–1067. 1998. View Article : Google Scholar : PubMed/NCBI | |
Pfeifer AM, Cole KE, Smoot DT, et al: Simian virus 40 large tumor antigen-immortalized normal human liver epithelial cells express hepatocyte characteristics and metabolize chemical carcinogens. Proc Natl Acad Sci USA. 90:5123–5127. 1993. View Article : Google Scholar | |
Fukaya K, Asahi S, Nagamori S, et al: Establishment of a human hepatocyte line (OUMS-29) having CYP 1A1 and 1A2 activities from fetal liver tissue by transfection of SV40 LT. In Vitro Cell Dev Biol Anim. 37:266–269. 2001. View Article : Google Scholar : PubMed/NCBI | |
Schaff Z, Kovalszky I, Nagy P, Zalatnai A, Jeney A and Lapis K: Human and experimental hepatocarcinogenesis. Scand J Gastroenterol (Suppl). 228:90–97. 1998. View Article : Google Scholar | |
Buchmann A, Ziegler S, Wolf A, Robertson LW, Durham SK and Schwarz M: Effects of polychlorinated biphenyls in rat liver: correlation between primary subcellular effects and promoting activity. Toxicol Appl Pharmacol. 111:454–468. 1991. View Article : Google Scholar | |
Jaworski M, Hailfinger S, Buchmann A, et al: Human p53 knock-in (hupki) mice do not differ in liver tumor response from their counterparts with murine p53. Carcinogenesis. 26:1829–1834. 2005. View Article : Google Scholar : PubMed/NCBI | |
Unger C, Buchmann A, Bunemann CL, Kress S and Schwarz M: Wild-type function of the p53 tumor suppressor protein is not required for apoptosis of mouse hepatoma cells. Cell Death Differ. 5:87–95. 1998. View Article : Google Scholar : PubMed/NCBI |