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Hepatocellular Carcinogenesis

  • Nicole Golob-Schwarzl
  • Sonja KesslerEmail author
  • Johannes Haybaeck
Chapter

Abstract

Please check if the section headings are assigned to appropriate levels.

Keywords

Squamous Cell Carcinoma Antigen Subcutaneous Xenograft Orthotopic Xenograft Golgi Protein Squamous Cell Carcinoma Antigen Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    International Agency for Research on Cancer. GLOBOCAN 2012: estimated cancer incidence, mortality and prevalence worldwide in 2012. Lyon: Inerational Agency for Research on Cancer; 2013.Google Scholar
  2. 2.
    Kim JH, Sohn BH, Lee HS, Kim SB, Yoo JE, et al. Genomic predictors for recurrence patterns of hepatocellular carcinoma: model derivation and validation. PLoS Med. 2014;11:e1001770.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    El Serga HB. Hepatocellular carcinoma: recent trends in the United States. Gastroenterology. 2004;127:S27–34.CrossRefGoogle Scholar
  4. 4.
    Davila JA, Morgan RO, Shaib Y, McGlynn KA, El Serage HB. Hepatitis C infection and the increasing incidence of hepatocellular carcinoma: a population-based study. Gastroenterology. 2004;127:1372–80.PubMedCrossRefGoogle Scholar
  5. 5.
    Imamura H, Matsuyama Y, Tanaka E, Ohkuba T, Hasegawa K, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol. 2003;38:200–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology. 1999;30:1434–40.PubMedCrossRefGoogle Scholar
  7. 7.
    Poon RT, Fan ST, Ng IO, Lo CM, Lui CL, et al. Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma. Cancer. 2000;89:500–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454:436–44.PubMedCrossRefGoogle Scholar
  9. 9.
    Bosch FX, Ribes J, Cleries R, Diaz M. Epidemiology of hepatocellular carcinoma. Clin Liver Dis. 2005;9:191–211.PubMedCrossRefGoogle Scholar
  10. 10.
    Sun B, Karin M. Inflammation and liver tumorigenesis. Front Med. 2013;7:242–54.PubMedCrossRefGoogle Scholar
  11. 11.
    Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986;315:1650–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Tsuchiya N, Sawada Y, Endo I, Saito K, Uemura Y, et al. Biomarkers for the early diagnosis of hepatocellular carcinoma. World J Gastroenterol. 2015;21:10573–83.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Tatarinov I, Tatarinov S. Detection of embryo-specific alpha-globulin in the blood serum of a patient with primary liver cancer. Vopr Med Khim. 1964;10:90–1.PubMedGoogle Scholar
  14. 14.
    Khattab M, Fouad M, Ahmed E. Role of biomarkers in the prediction and diagnosis of hepatocellular carcinoma. World J Hepatol. 2015;7:2474–81.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Hu B, Tian X, Sun J, Meng X. Evaluation of individual and combined applications of serum biomarkers for diagnosis of hepatocellular carcinoma: a meta-analysis. Int J Mol Sci. 2013;14:23559–80.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Trevisani F, DÍntino PE, Morselli-Labate AM, Mazzella G, Accogli G, et al. Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status. J Hepatol. 2001;34:570–5.PubMedCrossRefGoogle Scholar
  17. 17.
    Tsuchiya N, Sawada Y, Endo I, Saito K, Uemura Y, et al. Biomarkers for the early diagnosis of hepatocellular carcinoma. World J Gastroenterol. 2015;37:10573–83.CrossRefGoogle Scholar
  18. 18.
    Naraki T, Kohno N, Saito H, Fujimoto Y, Ohhira M, et al. Gamma-Carboxyglutamic acid content of hepatocellular carcinoma-associated des-gamma-carboxy prothrombin. Biochim Biophys Acta. 2002;1586:287–98.PubMedCrossRefGoogle Scholar
  19. 19.
    Libbrecht L, Severi T, Cassiman D, Vander Borght S, Pirenne J, et al. Glypican-3 expression distinguishes small hepatocellular carcinomas from cirrhosis, dysplastic nodules, and focal nodular hyperplasia-like nodules. Am J Surg Pathol. 2006;30:1405–11.PubMedCrossRefGoogle Scholar
  20. 20.
    Shafizadeh N, Ferrell LD, Kakar S. Utility and limitations of glypican-3 expression for the diagnosis of hepatocellular carcinoma at both ends of the differentiation spectrum. Mod Pathol. 2006;21:1011–8.CrossRefGoogle Scholar
  21. 21.
    Motomura Y, Senju S, Nakatsura T, Matsuyoshi H, Hirata S, et al. Embryonic stem cell-derived dendritic cells expressing glypican-3, a recently identified oncofetal antigen, induce protective immunity against highly metastatic mouse melanoma. Cancer Res. 2006;66:2414–22.PubMedCrossRefGoogle Scholar
  22. 22.
    Shevede LA, Das S, Clark DW, Samant RS. Osteopontin: an effector and an effect of tumor metastasis. Curr Mol Med. 2010;10:71–81.CrossRefGoogle Scholar
  23. 23.
    Kawashima R, Mochida S, Matsui A, YouLu TuZ Y, Ishikawa K, et al. Expression of osteopontin in Kupffer cells and hepatic macrophages and Stellate cells in rat liver after carbon tetrachloride intoxication: a possible factor for macrophage migration into hepatic necrotic areas. Biochem Biophys Res Commun. 1999;256:527–31.PubMedCrossRefGoogle Scholar
  24. 24.
    Shand S, Plymoth A, Ge S, Feng Z, Rosen HR, et al. Identification of osteopontin as a novel marker for early hepatocellular carcinoma. Hepatology. 2012;55:483–90.CrossRefGoogle Scholar
  25. 25.
    Kladney RD, Cui X, Bulla GA, Brunt EM, Fimmel CJ, et al. Expression of GP73, a resident Golgi membrane protein, in viral and nonviral liver disease. Hepatology. 2002;35:1431–40.PubMedCrossRefGoogle Scholar
  26. 26.
    Mao Y, Yang H, Xu H, Lu X, Sang X, et al. Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma. Gut. 2010;59:1687–93.PubMedCrossRefGoogle Scholar
  27. 27.
    Hu JS, Wu DW, Liang S, Miao XY. GP73, a resident Golgi glycoprotein, is sensibility and specificity for hepatocellular carcinoma of diagnosis in a hepatitis B-endemic Asian population. Med Oncol. 2010;27:339–45.PubMedCrossRefGoogle Scholar
  28. 28.
    Hussein MM, Ibrahim AA, Abdella HM, Montasser IF, Hassan MI. Evaluation of serum squamous cell carcinoma antigen as a novel biomarker for diagnosis of hepatocellular carcinoma in Egyptian patients. Indian J Cancer. 2008;45:167–72.PubMedCrossRefGoogle Scholar
  29. 29.
    Giannelli G, MArinosci F, Trerotoli P, Volpe A, Quaranta M, et al. SCCA antigen combined with alpha-fetoprotein as serologic marker of HCC. Int J Cancer. 2005;117:506–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Pontisso P, Quarta S, Caberlotto C, Beneduce L, Marino M, et al. Progressive increase of SCCA-IgM immune complexes in cirrhotic patients is associated with development of hepatocellular carcinoma. Int J Cancer. 2006;119:735–40.PubMedCrossRefGoogle Scholar
  31. 31.
    Sharma MC, Koltowski L, Ownbey RT, Tuszynski P, Sharam MC. Angiogenesis-associated protein annexin II in breast cancer: selective expression in invasive breast cancer and contribution to tumor invasion and progression. Exp Mol Pathol. 2006;81:146–56.PubMedCrossRefGoogle Scholar
  32. 32.
    Shiozawa Y, Havens AM, Jung Y, Ziegler AM, Pedersen EA, et al. Annexin II/annexin II receptor axis regulates adhesion, migration, homing, and growth of prostate cancer. J Cell Biochem. 2008;105:370–80.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Hollas H, Aukrust I, Grimmer S, Strand E, Flatmark T, et al. Annexin A2 recognises a specific region in the 3′-UTR of its cognate messenger RNA. Biochim Biophys Acta. 2006;1763:1325–34.PubMedCrossRefGoogle Scholar
  34. 34.
    Muramatsu T. Midkine and pleiotrophin: two related proteins involved in development, survival, inflammation and tumorigenesis. J Biochem. 2002;132:359–71.PubMedCrossRefGoogle Scholar
  35. 35.
    Shaheen KY, Abdel-Mageed AI, Safwat E, AlBreedy AM. The value of serum midkine level in diagnosis of hepatocellular carcinoma. Int J Hepatol. 2015;2015:146389.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Zhu WW, Guo L, Guo JJ, Jia HL, Zhu M, et al. Evaluation of midkine as a diagnostic serum biomarker in hepatocellular carcinoma. Clin Cancer Res. 2013;19:3944–54.PubMedCrossRefGoogle Scholar
  37. 37.
    Rankin EB, Fuh KC, Taylor TE, Krieg AJ, Musser M, et al. AXL is an essential factor and therapeutic target for metastatic ovarian cancer. Cancer Res. 2010;70:7570–9.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Reichl P, Fang M, Starlinger P, Staufer K, Nenutil R, et al. Multicenter analysis of soluble Axl reveals diagnostic value for very early stage hepatocellular carcinoma. Int J Cancer. 2015;137:385–94.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Nordberg J, Arnér ES. Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic Biol Med. 2001;31:1287–312.PubMedCrossRefGoogle Scholar
  40. 40.
    Kakolyris S, Giatromanolaki A, Koukourakis M, Powis G, Souglakos J, et al. Thioredoxin expression is associated with lymph node status and prognosis in early operable non-small cell lung cancer. Clin Cancer Res. 2001;7:3087–91.PubMedGoogle Scholar
  41. 41.
    Ferracin M, Veronese A, Negrini M. Micromarkers: miRNA in cancer diagnosis and prognosis. Expert Rev Mol Diagn. 2010;10:297–308.PubMedCrossRefGoogle Scholar
  42. 42.
    Schütte K, Schulz C, Link A, Malfertheiner P. Current biomarkers for hepatocellular carcinoma: surveillance, diagnosis and prediction of prognosis. World J Hepatol. 2015;7:139–49.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Murakami Y, Yasuda T, Saigo K, Urashima T, Toyoda H, et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene. 2006;25:2537–45.PubMedCrossRefGoogle Scholar
  44. 44.
    Zhou J, Yu L, Gao X, Hu J, Wang J, et al. Plasma microRNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma. J Clin Oncol. 2011;29:4781–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Abdalla MA, Haj-Ahmad Y. Promising candidate urinary microRNA Biomarkers for early detection of hepatocellular carcinoma among high-risk hepatitis C virus Egyptian patients. J Cancer. 2012;3:19–31.PubMedCrossRefGoogle Scholar
  46. 46.
    He L, Tian DA, Li PY, He XX. Mouse models of liver cancer: progress and recommendations. Oncotarget. 2015;6(27):23306–22. doi: 10.18632/oncotarget.4202.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Newell P, Villanueva A, Friedman SL, Koike K, Llovet JM. Experimental models of hepatocellular carcinoma. J Hepatol. 2008;48(5):858–79. doi: 10.1016/j.jhep.2008.01.008.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Bakiri L, Wagner EF. Mouse models for liver cancer. Mol Oncol. 2013;7(2):206–23. doi: 10.1016/j.molonc.2013.01.005.PubMedCrossRefGoogle Scholar
  49. 49.
    Li Y, Tang Z-Y, Hou J-X. Hepatocellular carcinoma: insight from animal models. Nat Rev Gastroenterol Hepatol. 2012;9(1):32–43.CrossRefGoogle Scholar
  50. 50.
    Kim SM, Im GH, Lee DG, Lee JH, Lee WJ, Lee IS. Mn(2+)-doped silica nanoparticles for hepatocyte-targeted detection of liver cancer in T1-weighted MRI. Biomaterials. 2013;34(35):8941–8. doi: 10.1016/j.biomaterials.2013.08.009.PubMedCrossRefGoogle Scholar
  51. 51.
    Baek S, Mueller A, Lim Y-S, Lee HC, Lee Y-J, Gong G, Kim JS, Ryu J-S, Oh SJ, Lee SJ, Bacher-Stier C, Fels L, Koglin N, Schatz CA, Dinkelborg LM, Moon DH. (4S)-4-(3-18F-fluoropropyl)-l-glutamate for imaging of xC transporter activity in hepatocellular carcinoma using PET: preclinical and exploratory clinical studies. J Nucl Med. 2013;54(1):117–23. doi: 10.2967/jnumed.112.108704.PubMedCrossRefGoogle Scholar
  52. 52.
    Matouk IJ, DeGroot N, Mezan S, Ayesh S, Abu-Lail R, Hochberg A, Galun E. The H19 non-coding RNA is essential for human tumor growth. PLoS One. 2007;2(9)Google Scholar
  53. 53.
    Zheng T, Yin D, Lu Z, Wang J, Li Y, Chen X, Liang Y, Song X, Qi S, Sun B, Xie C, Meng X, Pan S, Liu J, Jiang H, Liu L. Nutlin-3 overcomes arsenic trioxide resistance and tumor metastasis mediated by mutant p53 in Hepatocellular Carcinoma. Mol Cancer. 2014;13:133. doi: 10.1186/1476-4598-13-133.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Liu L, Cao Y, Chen C, Zhang X, McNabola A, Wilkie D, Wilhelm S, Lynch M, Carter C. Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res. 2006;66(24):11851–8. doi: 10.1158/0008-5472.CAN-06-1377.PubMedCrossRefGoogle Scholar
  55. 55.
    Fuchs BC, Fujii T, Dorfman JD, Goodwin JM, Zhu AX, Lanuti M, Tanabe KK. Epithelial-to-mesenchymal transition and integrin-linked kinase mediate sensitivity to epidermal growth factor receptor inhibition in human hepatoma cells. Cancer Res. 2008;68(7):2391–9. doi: 10.1158/0008-5472.can-07-2460.PubMedCrossRefGoogle Scholar
  56. 56.
    Li Y, Yu DC, Chen Y, Amin P, Zhang H, Nguyen N, Henderson DR. A hepatocellular carcinoma-specific adenovirus variant, CV890, eliminates distant human liver tumors in combination with doxorubicin. Cancer Res. 2001;61(17):6428–36.PubMedGoogle Scholar
  57. 57.
    Pei Z, Chu L, Zou W, Zhang Z, Qiu S, Qi R, Gu J, Qian C, Liu X. An oncolytic adenoviral vector of Smac increases antitumor activity of TRAIL against HCC in human cells and in mice. Hepatology. 2004;39(5):1371–81. doi: 10.1002/hep.20203.PubMedCrossRefGoogle Scholar
  58. 58.
    Yoo BK, Emdad L, Su ZZ, Villanueva A, Chiang DY, Mukhopadhyay ND, Mills AS, Waxman S, Fisher RA, Llovet JM, Fisher PB, Sarkar D. Astrocyte elevated gene-1 regulates hepatocellular carcinoma development and progression. J Clin Invest. 2009;119(3):465–77. doi: 10.1172/JCI36460.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Chen L-D, Liu J, Yu X-F, He M, Pei X-F, Tang Z-Y, Wang Q-Q, Pang D-W, Li Y. The biocompatibility of quantum dot probes used for the targeted imaging of hepatocellular carcinoma metastasis. Biomaterials. 2008;29(31):4170–6.PubMedCrossRefGoogle Scholar
  60. 60.
  61. 61.
    Chen K-F, Yeh P-Y, Yeh K-H, Lu Y-S, Huang S-Y, Cheng A-L. Down-regulation of phospho-Akt is a major molecular determinant of bortezomib-induced apoptosis in hepatocellular carcinoma cells. Cancer Res. 2008;68(16):6698–707. doi: 10.1158/0008-5472.can-08-0257.PubMedCrossRefGoogle Scholar
  62. 62.
    Hu J, Dong A, Fernandez-Ruiz V, Shan J, Kawa M, Martinez-Anso E, Prieto J, Qian C. Blockade of Wnt signaling inhibits angiogenesis and tumor growth in hepatocellular carcinoma. Cancer Res. 2009;69(17):6951–9. doi: 10.1158/0008-5472.CAN-09-0541.PubMedCrossRefGoogle Scholar
  63. 63.
    Zhu LM, Shi DM, Dai Q, Cheng XJ, Yao WY, Sun PH, Ding Y, Qiao MM, Wu YL, Jiang SH, Tu SP. Tumor suppressor XAF1 induces apoptosis, inhibits angiogenesis and inhibits tumor growth in hepatocellular carcinoma. Oncotarget. 2014;5(14):5403–15.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Peng H, Dara L, Li TW, Zheng Y, Yang H, Tomasi ML, Tomasi I, Giordano P, Mato JM, Lu SC. MAT2B-GIT1 interplay activates MEK1/ERK 1 and 2 to induce growth in human liver and colon cancer. Hepatology. 2013;57(6):2299–313. doi: 10.1002/hep.26258.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Yao X, Hu JF, Daniels M, Yien H, Lu H, Sharan H, Zhou X, Zeng Z, Li T, Yang Y, Hoffman AR. A novel orthotopic tumor model to study growth factors and oncogenes in hepatocarcinogenesis. Clin Cancer Res. 2003;9(7):2719–26.PubMedGoogle Scholar
  66. 66.
    Yang XZ, Dou S, Sun TM, Mao CQ, Wang HX, Wang J. Systemic delivery of siRNA with cationic lipid assisted PEG-PLA nanoparticles for cancer therapy. J Control Release. 2011;156(2):203–11. doi: 10.1016/j.jconrel.2011.07.035.PubMedCrossRefGoogle Scholar
  67. 67.
    Wang R, Zhao N, Li S, Fang JH, Chen MX, Yang J, Jia WH, Yuan Y, Zhuang SM. MicroRNA-195 suppresses angiogenesis and metastasis of hepatocellular carcinoma by inhibiting the expression of VEGF, VAV2, and CDC42. Hepatology. 2013;58(2):642–53. doi: 10.1002/hep.26373.PubMedCrossRefGoogle Scholar
  68. 68.
    Yan XL, Jia YL, Chen L, Zeng Q, Zhou JN, Fu CJ, Chen HX, Yuan HF, Li ZW, Shi L, Xu YC, Wang JX, Zhang XM, He LJ, Zhai C, Yue W, Pei XT. Hepatocellular carcinoma-associated mesenchymal stem cells promote hepatocarcinoma progression: role of the S100A4-miR155-SOCS1-MMP9 axis. Hepatology. 2013;57(6):2274–86. doi: 10.1002/hep.26257.PubMedCrossRefGoogle Scholar
  69. 69.
    Gauttier V, Judor JP, Le Guen V, Cany J, Ferry N, Conchon S. Agonistic anti-CD137 antibody treatment leads to antitumor response in mice with liver cancer. Int J Cancer. 2014;135(12):2857–67. doi: 10.1002/ijc.28943.PubMedCrossRefGoogle Scholar
  70. 70.
    McIlroy D, Barteau B, Cany J, Richard P, Gourden C, Conchon S, Pitard B. DNA/amphiphilic block copolymer nanospheres promote low-dose DNA vaccination. Mol Ther. 2009;17(8):1473–81. doi: 10.1038/mt.2009.84.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Avella DM, Li G, Schell TD, Liu D, Zhang SSM, Lou X, Berg A, Kimchi ET, Tagaram HRS, Yang Q, Shereef S, Garcia LS, Kester M, Isom HC, Rountree CB, Staveley-O’Carroll KF. Regression of established hepatocellular carcinoma is induced by chemoimmunotherapy in an orthotopic murine model. Hepatology. 2012;55(1):141–52. doi: 10.1002/hep.24652.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Zhao W, Zhang L, Xu Y, Zhang Z, Ren G, Tang K, Kuang P, Zhao B, Yin Z, Wang X. Hepatic stellate cells promote tumor progression by enhancement of immunosuppressive cells in an orthotopic liver tumor mouse model. Lab Invest. 2014;94(2):182–91. doi: 10.1038/labinvest.2013.139.PubMedCrossRefGoogle Scholar
  73. 73.
    Kornek M, Lukacs-Kornek V, Limmer A, Raskopf E, Becker U, Klockner M, Sauerbruch T, Schmitz V. 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)-formulated, immune-stimulatory vascular endothelial growth factor a small interfering RNA (siRNA) increases antitumoral efficacy in murine orthotopic hepatocellular carcinoma with liver fibrosis. Mol Med. 2008;14(7–8):365–73. doi: 10.2119/2008-00003.Kornek.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Pitot HC, Dragan YP. Facts and theories concerning the mechanisms of carcinogenesis. FASEB J. 1991;5(9):2280–6.PubMedGoogle Scholar
  75. 75.
    Rajewsky MF, Dauber W, Frankenberg H. Liver carcinogenesis by diethylnitrosamine in the rat. Science. 1966;152(3718):83–5.PubMedCrossRefGoogle Scholar
  76. 76.
    Solt DB, Medline A, Farber E. Rapid emergence of carcinogen-induced hyperplastic lesions in a new model for the sequential analysis of liver carcinogenesis. Am J Pathol. 1977;88(3):595–618.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Farber E, Sarma DS. Hepatocarcinogenesis: a dynamic cellular perspective. Lab Invest. 1987;56(1):4–22.PubMedGoogle Scholar
  78. 78.
    Diwan BA, Rice JM, Ohshima M, Ward JM. Interstrain differences in susceptibility to liver carcinogenesis initiated by N-nitrosodiethylamine and its promotion by phenobarbital in C57BL/6NCr, C3H/HeNCrMTV- and DBA/2NCr mice. Carcinogenesis. 1986;7(2):215–20.PubMedCrossRefGoogle Scholar
  79. 79.
    Vesselinovitch SD, Mihailovich N. Kinetics of diethylnitrosamine hepatocarcinogenesis in the infant mouse. Cancer Res. 1983;43(9):4253–9.PubMedGoogle Scholar
  80. 80.
    McCay PB, Lai EK, Poyer JL, DuBose CM, Janzen EG. Oxygen- and carbon-centered free radical formation during carbon tetrachloride metabolism. Observation of lipid radicals in vivo and in vitro. J Biol Chem. 1984;259(4):2135–43.PubMedGoogle Scholar
  81. 81.
    Ghoshal AK, Ahluwalia M, Farber E. The rapid induction of liver cell death in rats fed a choline-deficient methionine-low diet. Am J Pathol. 1983;113(3):309–14.PubMedPubMedCentralGoogle Scholar
  82. 82.
    Li X, Benjamin IS, Alexander B. Reproducible production of thioacetamide-induced macronodular cirrhosis in the rat with no mortality. J Hepatol. 2002;36(4):488–93.PubMedCrossRefGoogle Scholar
  83. 83.
    Rushmore TH, Ghazarian DM, Subrahmanyan V, Farber E, Ghoshal AK. Probable free radical effects on rat liver nuclei during early hepatocarcinogenesis with a choline-devoid low methionine diet. Cancer Res. 1987;47(24 Pt 1):6731–40.PubMedGoogle Scholar
  84. 84.
    Coulouarn C, Gomez-Quiroz LE, Lee J-S, Kaposi-Novak P, Conner EA, Goldina TA, Onishchenko GE, Factor VM, Thorgeirsson SS. Oncogene-specific gene expression signatures at preneoplastic stage in mice define distinct mechanisms of hepatocarcinogenesis. Hepatology. 2006;44(4):1003–11. doi: 10.1002/hep.21293.PubMedCrossRefGoogle Scholar
  85. 85.
    Groos J, Bannasch P, Schwarz M, Kopp-Schneider A. Comparison of mode of action of four hepatocarcinogens: a model-based approach. Toxicol Sci. 2007;99(2):446–54. doi: 10.1093/toxsci/kfm183.PubMedCrossRefGoogle Scholar
  86. 86.
    Lee JS, Chu IS, Mikaelyan A, Calvisi DF, Heo J, Reddy JK, Thorgeirsson SS. Application of comparative functional genomics to identify best-fit mouse models to study human cancer. Nat Genet. 2004;36(12):1306–11. doi: 10.1038/ng1481.PubMedCrossRefGoogle Scholar
  87. 87.
    Poirier LA. Hepatocarcinogenesis by diethylnitrosamine in rats fed high dietary levels of lipotropes. J Natl Cancer Inst. 1975;54(1):137–40.PubMedCrossRefGoogle Scholar
  88. 88.
    Tamano S, Merlino GT, Ward JM. Rapid development of hepatic tumors in transforming growth factor alpha transgenic mice associated with increased cell proliferation in precancerous hepatocellular lesions initiated by N-nitrosodiethylamine and promoted by phenobarbital. Carcinogenesis. 1994;15(9):1791–8.PubMedCrossRefGoogle Scholar
  89. 89.
    Yaswen P, Goyette M, Shank PR, Fausto N. Expression of c-Ki-ras, c-Ha-ras, and c-myc in specific cell types during hepatocarcinogenesis. Mol Cell Biol. 1985;5(4):780–6.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Nagy P, Evarts RP, Marsden E, Roach J, Thorgeirsson SS. Cellular distribution of c-myc transcripts during chemical hepatocarcinogenesis in rats. Cancer Res. 1988;48(19):5522–7.PubMedGoogle Scholar
  91. 91.
    Rao MS, Lalwani ND, Watanabe TK, Reddy JK. Inhibitory effect of antioxidants ethoxyquin and 2(3)-tert-butyl-4-hydroxyanisole on hepatic tumorigenesis in rats fed ciprofibrate, a peroxisome proliferator. Cancer Res. 1984;44(3):1072–6.PubMedGoogle Scholar
  92. 92.
    Sakurai T, Kudo M, Umemura A, He G, Elsharkawy AM, Seki E, Karin M. p38α inhibits liver fibrogenesis and consequent hepatocarcinogenesis by curtailing accumulation of reactive oxygen species. Cancer Res. 2013;73(1):215–24. doi: 10.1158/0008-5472.can-12-1602.PubMedCrossRefGoogle Scholar
  93. 93.
    Fujii T, Fuchs BC, Yamada S, Lauwers GY, Kulu Y, Goodwin JM, Lanuti M, Tanabe KK. Mouse model of carbon tetrachloride induced liver fibrosis: histopathological changes and expression of CD133 and epidermal growth factor. BMC Gastroenterol. 2010;10(1):1–11. doi: 10.1186/1471-230x-10-79.CrossRefGoogle Scholar
  94. 94.
    Ghebranious N, Sell S. The mouse equivalent of the human p53ser249 mutation p53ser246 enhances aflatoxin hepatocarcinogenesis in hepatitis B surface antigen transgenic and p53 heterozygous null mice. Hepatology. 1998;27(4):967–73. doi: 10.1002/hep.510270411.PubMedCrossRefGoogle Scholar
  95. 95.
    Tuveson DA, Jacks T. Technologically advanced cancer modeling in mice. Curr Opin Genet Dev. 2002;12(1):105–10. doi: 10.1016/S0959-437X(01)00272-6.PubMedCrossRefGoogle Scholar
  96. 96.
    Frese KK, Tuveson DA. Maximizing mouse cancer models. Nat Rev Cancer. 2007;7(9):645–58. doi: 10.1038/nrc2192.PubMedCrossRefGoogle Scholar
  97. 97.
    Kamegaya Y, Hiasa Y, Zukerberg L, Fowler N, Blackard JT, Lin W, Choe WH, Schmidt EV, Chung RT. Hepatitis C virus acts as a tumor accelerator by blocking apoptosis in a mouse model of hepatocarcinogenesis. Hepatology. 2005;41(3):660–7. doi: 10.1002/hep.20621.PubMedCrossRefGoogle Scholar
  98. 98.
    Lerat H, Honda M, Beard MR, Loesch K, Sun J, Yang Y, Okuda M, Gosert R, Xiao S, Weinman SA, Lemon SM. Steatosis and liver cancer in transgenic mice expressing the structural and nonstructural proteins of hepatitis C virus. Gastroenterology. 2002;122(2):352–65.PubMedCrossRefGoogle Scholar
  99. 99.
    Jhappan C, Stahle C, Harkins RN, Fausto N, Smith GH, Merlino GT. TGFα overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas. Cell. 1990;61(6):1137–46. doi: 10.1016/0092-8674(90)90076-Q.PubMedCrossRefGoogle Scholar
  100. 100.
    Lou DQ, Molina T, Bennoun M, Porteu A, Briand P, Joulin V, Vasseur-Cognet M, Cavard C. Conditional hepatocarcinogenesis in mice expressing SV 40 early sequences. Cancer Lett. 2005;229(1):107–14. doi: 10.1016/j.canlet.2004.12.032.PubMedCrossRefGoogle Scholar
  101. 101.
    Shachaf CM, Kopelman AM, Arvanitis C, Karlsson Å, Beer S, Mandl S, Bachmann MH, Borowsky AD, Ruebner B, Cardiff RD, Yang Q, Bishop JM, Contag CH, Felsher DW. MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature. 2004;431(7012):1112–7. doi: 10.1038/nature03043.PubMedCrossRefGoogle Scholar
  102. 102.
    Chisari FV, Filippi P, Buras J, McLachlan A, Popper H, Pinkert CA, Palmiter RD, Brinster RL. Structural and pathological effects of synthesis of hepatitis B virus large envelope polypeptide in transgenic mice. Proc Natl Acad Sci U S A. 1987;84(19):6909–13.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Chisari FV, Klopchin K, Moriyama T, Pasquinelli C, Dunsford HA, Sell S, Pinkert CA, Brinster RL, Palmiter RD. Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice. Cell. 1989;59(6):1145.PubMedCrossRefGoogle Scholar
  104. 104.
    Chisari FV, Pinkert CA, Milich DR, Filippi P, McLachlan A, Palmiter RD, Brinster RL. A transgenic mouse model of the chronic hepatitis B surface antigen carrier state. Science. 1985;230(4730):1157–60.PubMedCrossRefGoogle Scholar
  105. 105.
    Koike K, Moriya K, Iino S, Yotsuyanagi H, Endo Y, Miyamura T, Kurokawa K. High-level expression of hepatitis B virus HBx gene and hepatocarcinogenesis in transgenic mice. Hepatology. 1994;19(4):810–9.PubMedCrossRefGoogle Scholar
  106. 106.
    Toshkov I, Chisari FV, Bannasch P. Hepatic preneoplasia in hepatitis B virus transgenic mice. Hepatology. 1994;20(5):1162–72. doi: 10.1016/0270-9139(94)90752-8.PubMedCrossRefGoogle Scholar
  107. 107.
    Koike K, Moriya K, Kimura S. Role of hepatitis C virus in the development of hepatocellular carcinoma: transgenic approach to viral hepatocarcinogenesis. J Gastroenterol Hepatol. 2002;17(4):394–400. doi: 10.1046/j.1440-1746.2002.02763.x.PubMedCrossRefGoogle Scholar
  108. 108.
    Fan CY, Pan J, Usuda N, Yeldandi AV, Rao MS, Reddy JK. Steatohepatitis, spontaneous peroxisome proliferation and liver tumors in mice lacking peroxisomal fatty acyl-Coa oxidase: implications for peroxisome proliferator-activated receptor α natural ligand metabolism. J Biol Chem. 1998;273(25):15639–45. doi: 10.1074/jbc.273.25.15639.PubMedCrossRefGoogle Scholar
  109. 109.
    Geller SA, Nichols WS, Kim S, Tolmachoff T, Lee S, Dycaico MJ, Felts K, Sorge JA. Hepatocarcinogenesis is the sequel to hepatitis in Z#2 α1-antitrypsin transgenic mice: histopathological and DNA ploidy studies. Hepatology. 1994;19(2):389–97.PubMedCrossRefGoogle Scholar
  110. 110.
    Colnot S, Decaens T, Niwa-Kawakita M, Godard C, Hamard G, Kahn A, Giovannini M, Perret C. Liver-targeted disruption of Apc in mice activates β-catenin signaling and leads to hepatocellular carcinomas. Proc Natl Acad Sci U S A. 2004;101(49):17216–21. doi: 10.1073/pnas.0404761101.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Harada N, Oshima H, Katoh M, Tamai Y, Oshima M, Taketo MM. Hepatocarcinogenesis in mice with β-catenin and Ha-ras gene mutations. Cancer Res. 2004;64(1):48–54. doi: 10.1158/0008-5472.CAN-03-2123.PubMedCrossRefGoogle Scholar
  112. 112.
    Conner EA, Lemmer ER, Sánchez A, Factor VM, Thorgeirsson SS. E2F1 blocks and c-Myc accelerates hepatic ploidy in transgenic mouse models. Biochem Biophys Res Commun. 2003;302(1):114–20. doi: 10.1016/S0006-291X(03)00125-6.PubMedCrossRefGoogle Scholar
  113. 113.
    Dalemans W, Perraud F, Le Meur M, Gerlinger P, Courthey M, Pavirani A. Heterologous protein expression by transimmortalized differentiated liver cell lines derived from transgenic mice (hepatomas/α1 antitrypsin/ONC mouse). Biologicals. 1990;18(3):191–8. doi: 10.1016/1045-1056(90)90006-L.PubMedCrossRefGoogle Scholar
  114. 114.
    Perraud F, Dalemans W, Gendrault JL, Dreyer D, Ali-Hadji D, Faure T, Pavirani A. Characterization of trans-immortalized hepatic cell lines established from transgenic mice. Exp Cell Res. 1991;195(1):59–65. doi: 10.1016/0014-4827(91)90500-T.PubMedCrossRefGoogle Scholar
  115. 115.
    Sandgren EP, Quaife CJ, Pinkert CA, Palmiter RD, Brinster RL. Oncogene-induced liver neoplasia in transgenic mice. Oncogene. 1989;4(6):715–24.PubMedGoogle Scholar
  116. 116.
    Santoni-Rugiu E, Nagy P, Jensen MR, Factor VM, Thorgeirsson SS. Evolution of neoplastic development in the liver of transgenic mice co- expressing c-myc and transforming growth factor-α. Am J Pathol. 1996;149(2):407–28.PubMedPubMedCentralGoogle Scholar
  117. 117.
    Santoni-Rugiu E, Jensen MR, Thorgeirsson SS. Disruption of the pRb/E2F pathway and inhibition of apoptosis are major oncogenic events in liver constitutively expressing c-myc and transforming growth factor α. Cancer Res. 1998;58(1):123–34.PubMedGoogle Scholar
  118. 118.
    Murakami H, Sanderson ND, Nagy P, Marino PA, Merlino G, Thorgeirsson SS. Transgenic mouse model for synergistic effects of nuclear oncogenes and growth factors in tumorigenesis: interaction of c-myc and transforming growth factor α in hepatic oncogenesis. Cancer Res. 1993;53(8):1719–23.PubMedGoogle Scholar
  119. 119.
    Conner EA, Lemmer ER, Omori M, Wirth PJ, Factor VM, Thorgeirsson SS. Dual functions of E2F-1 in a transgenic mouse model of liver carcinogenesis. Oncogene. 2000;19(44):5054–62.PubMedCrossRefGoogle Scholar
  120. 120.
    Tonjes RR, Lohler J, O’Sullivan JF, Kay GF, Schmidt GH, Dalemans W, Pavirani A, Paul D. Autocrine mitogen IgEGF cooperates with c-myc or with the Hcs locus during hepatocarcinogenesis in transgenic mice. Oncogene. 1995;10(4):765–8.PubMedGoogle Scholar
  121. 121.
    Kitisin K, Ganesan N, Tang Y, Jogunoori W, Volpe EA, Kim SS, Katuri V, Kallakury B, Pishvaian M, Albanese C, Mendelson J, Zasloff M, Rashid A, Fishbein T, Evans SRT, Sidawy A, Reddy EP, Mishra B, Johnson LB, Shetty K, Mishra L. Disruption of transforming growth factor-β signaling through β-spectrin ELF leads to hepatocellular cancer through cyclin D1 activation. Oncogene. 2007;26(50):7103–10. doi: 10.1038/sj.onc.1210513.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Tang Y, Katuri V, Dillner A, Mishra B, Deng CX, Mishra L. Disruption of transforming growth factor-β signaling in ELF β-spectrin-deficient mice. Science. 2003;299(5606):574–7. doi: 10.1126/science.1075994.PubMedCrossRefGoogle Scholar
  123. 123.
    Sakata H, Takayama H, Sharp R, Rubin JS, Merlino G, LaRochelle WJ. Hepatocyte growth factor/scatter factor overexpression induces growth, abnormal development, and tumor formation in transgenic mouse livers. Cell Growth Differ. 1996;7(11):1513–23.PubMedGoogle Scholar
  124. 124.
    Shiota G, Wang TC, Nakamura T, Schmidt EV. Hepatocyte growth factor in transgenic mice: effects on hepatocyte growth, liver regeneration and gene expression. Hepatology. 1994;19(4):962–72.PubMedCrossRefGoogle Scholar
  125. 125.
    Santoni-Rugiu E, Preisegger KH, Kiss A, Audolfsson T, Shiota G, Schmidt EV, Thorgeirsson SS. Inhibition of neoplastic development in the liver by hepatocyte growth factor in a transgenic mouse model. Proc Natl Acad Sci U S A. 1996;93(18):9577–82. doi: 10.1073/pnas.93.18.9577.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Shiota G, Kawasaki H, Nakamura T, Schmidt EV. Characterization of double transgenic mice expressing hepatocyte growth factor and transforming growth factor α. Res Commun Mol Pathol Pharmacol. 1995;90(1):17–24.PubMedGoogle Scholar
  127. 127.
    Rogler CE, Yang D, Rossetti L, Donohoe J, Alt E, Chang CJ, Rosenfeld R, Neely K, Hintz R. Altered body composition and increased frequency of diverse malignancies in insulin-like growth factor-II transgenic mice. J Biol Chem. 1994;269(19):13779–84.PubMedGoogle Scholar
  128. 128.
    Harris TM, Rogler LE, Rogler CE. Reactivation of the maternally imprinted IGF2 allele in TGFα induced hepatocellular carcinomas in mice. Oncogene. 1998;16(2):203–9.PubMedCrossRefGoogle Scholar
  129. 129.
    Haybaeck J, Zeller N, Wolf MJ, Weber A, Wagner U, Kurrer MO, Bremer J, Iezzi G, Graf R, Clavien P-A, Thimme R, Blum H, Nedospasov SA, Zatloukal K, Ramzan M, Ciesek S, Pietschmann T, Marche PN, Karin M, Kopf M, Browning JL, Aguzzi A, Heikenwalder M. A lymphotoxin-driven pathway to hepatocellular carcinoma. Cancer Cell. 2009;16(4):295.PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Katzenellenbogen M, Pappo O, Barash H, Klopstock N, Mizrahi L, Olam D, Jacob-Hirsch J, Amariglio N, Rechavi G, Mitchell LA, Kohen R, Domany E, Galun E, Goldenberg D. Multiple adaptive mechanisms to chronic liver disease revealed at early stages of liver carcinogenesis in the Mdr2-knockout mice. Cancer Res. 2006;66(8):4001–10. doi: 10.1158/0008-5472.CAN-05-2937.PubMedCrossRefGoogle Scholar
  131. 131.
    Mauad TH, CMJ VN, Dingemans KP, JJM S, Schinkel AH, RGE N, Van Den Bergh Weerman MA, Verkruisen RP, Groen AK, RPJ OE, Van Der Valk MA, Borst P, GJA O. Mice with homozygous disruption of the mdr2 P-glycoprotein gene a novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis. Am J Pathol. 1994;145(5):1237–45.PubMedPubMedCentralGoogle Scholar
  132. 132.
    Tward AD, Jones KD, Yant S, Siu TC, Sheung TF, Chen X, Kay MA, Wang R, Bishop JM. Distinct pathways of genomic progression to benign and malignant tumors of the liver. Proc Natl Acad Sci U S A. 2007;104(37):14771–6. doi: 10.1073/pnas.0706578104.PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Wang R, Ferrell LD, Faouzi S, Maher JJ, Michael Bishop J. Activation of the Met receptor by cell attachment induces and sustains hepatocellular carcinomas in transgenic mice. J Cell Biol. 2001;153(5):1023–33. doi: 10.1083/jcb.153.5.1023.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Takami T, Kaposi-Novak P, Uchida K, Gomez-Quiroz LE, Conner EA, Factor VM, Thorgeirsson SS. Loss of hepatocyte growth factor/c-Met signaling pathway accelerates early stages of N-nitrosodiethylamine-induced hepatocarcinogenesis. Cancer Res. 2007;67(20):9844–51. doi: 10.1158/0008-5472.CAN-07-1905.PubMedCrossRefGoogle Scholar
  135. 135.
    Jacks T, Remington L, Williams BO, Schmitt EM, Halachmi S, Bronson RT, Weinberg RA. Tumor spectrum analysis in p53-mutant mice. Curr Biol. 1994;4(1):1–7. doi: 10.1016/S0960-9822(00)00002-6.PubMedCrossRefGoogle Scholar
  136. 136.
    Lewis BC, Klimstra DS, Socci ND, Xu S, Koutcher JA, Varmus HE. The absence of p53 promotes metastasis in a novel somatic mouse model for hepatocellular carcinoma. Mol Cell Biol. 2005;25(4):1228–37. doi: 10.1128/MCB.25.4.1228-1237.2005.PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Chen YW, Klimstra DS, Mongeau ME, Tatem JL, Boyartchuk V, Lewis BC. Loss of p53 and Ink4a/Arf cooperate in a cell autonomous fashion to induce metastasis of hepatocellular carcinoma cells. Cancer Res. 2007;67(16):7589–96. doi: 10.1158/0008-5472.CAN-07-0381.PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Xue W, Zender L, Miething C, Dickins RA, Hernando E, Krizhanovsky V, Cordon-Cardo C, Lowe SW. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature. 2007;445(7128):656–60. doi: 10.1038/nature05529.PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Campbell JS, Hughes SD, Gilbertson DG, Palmer TE, Holdren MS, Haran AC, Odell MM, Bauer RL, Ren HP, Haugen HS, Yeh MM, Fausto N. Platelet-derived growth factor C induces liver fibrosis, steatosis, and hepatocellular carcinoma. Proc Natl Acad Sci U S A. 2005;102(9):3389–94. doi: 10.1073/pnas.0409722102.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Horie Y, Suzuki A, Kataoka E, Sasaki T, Hamada K, Sasaki J, Mizuno K, Hasegawa G, Kishimoto H, Iizuka M, Naito M, Enomoto K, Watanabe S, Mak TW, Nakano T. Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas. J Clin Invest. 2004;113(12):1774.PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Watanabe S, Horie Y, Kataoka E, Sato W, Dohmen T, Ohshima S, Goto T, Suzuki A. Non-alcoholic steatohepatitis and hepatocellular carcinoma: lessons from hepatocyte-specific phosphatase and tensin homolog (PTEN)-deficient mice. J Gastroenterol Hepatol. 2007;22(Suppl. 1):S96–S100. doi: 10.1111/j.1440-1746.2006.04665.x.PubMedCrossRefGoogle Scholar
  142. 142.
    Dubois N, Bennoun M, Allemand I, Molina T, Grimber G, Daudet-Monsac M, Abelanet R, Briand P. Time-course development of differentiated hepatocarcinoma and lung metastasis in transgenic mice. J Hepatol. 1991;13(2):227–39. doi: 10.1016/0168-8278(91)90819-W.PubMedCrossRefGoogle Scholar
  143. 143.
    Manickan E, Satoi J, Wang TC, Liang TJ. Conditional liver-specific expression of simian virus 40 T antigen leads to regulatable development of hepatic neoplasm in transgenic mice. J Biol Chem. 2001;276(17):13989–94.PubMedCrossRefGoogle Scholar
  144. 144.
    Messing A, Chen HY, Palmiter RD, Brinster RL. Peripheral neuropathies, hepatocellular carcinomas and islet cell adenomas in transgenic mice. Nature. 1985;316(6027):461–3. doi: 10.1038/316461a0.PubMedCrossRefGoogle Scholar
  145. 145.
    Schirmacher P, Held WA, Yang D, Biempica L, Rogler CE. Selective amplification of periportal transitional cells precedes formation of hepatocellular carcinoma in SV40 large tag transgenic mice. Am J Pathol. 1991;139(1):231–41.PubMedPubMedCentralGoogle Scholar
  146. 146.
    Sepulveda AR, Finegold MJ, Smith B, Slagle BL, DeMayo JL, Shen RF, Woo SLC, Butel JS. Development of a transgenic mouse system for the analysis of stages in liver carcinogenesis using tissue-specific expression of SV40 large T-antigen controlled by regulatory elements of the human α-1-antitrypsin gene. Cancer Res. 1989;49(21):6108–17.PubMedGoogle Scholar
  147. 147.
    Farazi PA, Glickman J, Horner J, DePinho RA. Cooperative interactions of p53 mutation, telomere dysfunction, and chronic liver damage in hepatocellular carcinoma progression. Cancer Res. 2006;66(9):4766–73. doi: 10.1158/0008-5472.CAN-05-4608.PubMedCrossRefGoogle Scholar
  148. 148.
    Lee GH, Merlino G, Fausto N. Development of liver tumors in transforming growth factor α transgenic mice. Cancer Res. 1992;52(19):5162–70.PubMedGoogle Scholar
  149. 149.
    Sandgren EP, Luetteke NC, Palmiter RD, Brinster RL, Lee DC. Overexpression of TGFα in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast. Cell. 1990;61(6):1121–35. doi: 10.1016/0092-8674(90)90075-.PubMedCrossRefGoogle Scholar
  150. 150.
    Sanderson N, Factor V, Nagy P, Kopp J, Kondaiah P, Wakefield L, Roberts AB, Sporn MB, Thorgeirsson SS. Hepatic expression of mature transforming growth factor β1 in transgenic mice results in multiple tissue lesions. Proc Natl Acad Sci U S A. 1995;92(7):2572–6. doi: 10.1073/pnas.92.7.2572.PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Schnur J, Nagy P, Sebestyén A, Schaff Z, Thorgeirsson SS. Chemical hepatocarcinogenesis in transgenic mice overexpressing mature TGFβ-1 in liver. Eur J Cancer. 1999;35(13):1842–5. doi: 10.1016/S0959-8049(99)00224-5.PubMedCrossRefGoogle Scholar
  152. 152.
    Schnur J, Oláh J, Szepesi Á, Nagy P, Thorgeirsson SS. Thioacetamide-induced hepatic fibrosis in transforming growth factor beta-1 transgenic mice. Eur J Gastroenterol Hepatol. 2004;16(2):127–33. doi: 10.1097/00042737-200402000-00002.PubMedCrossRefGoogle Scholar
  153. 153.
    Soga M, Kishimoto Y, Kawamura Y, Inagaki S, Makino S, Saibara T. Spontaneous development of hepatocellular carcinomas in the FLS mice with hereditary fatty liver. Cancer Lett. 2003;196(1):43–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Nicole Golob-Schwarzl
    • 1
  • Sonja Kessler
    • 2
    Email author
  • Johannes Haybaeck
    • 3
    • 1
  1. 1.Institute of PathologyMedical University of GrazGrazAustria
  2. 2.Department of Pharmacy, Pharmaceutical BiologySaarland UniversitySaarbrueckenGermany
  3. 3.Department of PathologyMedical Faculty, Otto von Guericke University MagdeburgMagdeburgGermany

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