Synergistic function of Kras mutation and HBx in initiation and progression of hepatocellular carcinoma in mice

Oncogene

Volumn 33, Issue 43, 2014, Pages 5133-5138

  Ye, H ^a,b   Zhang, C ^a,b   Wang, B J ^b   Tan, X H ^b   Zhang, W P ^c   Teng, Y ^b   Yang, X ^a,b  

^a SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE   (China)

^b BEIJING INSTITUTE OF BIOTECHNOLOGY   (China)

^c SECOND MILITARY MEDICAL UNIVERSITY   (China)

Author keywords

Cre LoxP; HBx; hepatocellular carcinoma; KrasG12D; mouse model; transgenic mice

Indexed keywords

HEPATITIS B VIRUS X PROTEIN; KRAS2 PROTEIN, MOUSE; PROTEIN P21; TRANSACTIVATOR PROTEIN;

ANIMAL; C57BL MOUSE; CELL PROLIFERATION; GENE EXPRESSION REGULATION; GENETICS; LIVER CELL CARCINOMA; LIVER TUMOR; METABOLISM; MOUSE; MUTATION; PATHOLOGY; SIGNAL TRANSDUCTION; TRANSGENIC MOUSE;

ANIMALS; CARCINOMA, HEPATOCELLULAR; CELL PROLIFERATION; GENE EXPRESSION REGULATION, NEOPLASTIC; LIVER NEOPLASMS; MAP KINASE SIGNALING SYSTEM; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MUTATION; PROTO-ONCOGENE PROTEINS P21(RAS); TRANS-ACTIVATORS;

EID: 85027951114     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2013.468     Document Type: Article

References (45)

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61: 69–90. DOI: 10.3322/caac.20107
2. Arzumanyan A, Reis HM, Feitelson MA. Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma. Nat Rev Cancer 2012; 13: 123–135. DOI: 10.1038/nrc3449
3. Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer 2006; 6: 674–687. DOI: 10.1038/nrc1934
4. Morris SM, Baek JY, Koszarek A, Kanngurn S, Knoblaugh SE, Grady WM. Transforming growth factor-beta signaling promotes hepatocarcinogenesis induced by p53 loss. Hepatology 2012; 55: 121–131. DOI: 10.1002/hep.24653
5. Terradillos O, Billet O, Renard CA, Levy R, Molina T, Briand P et al. The hepatitis B virus X gene potentiates c-myc-induced liver oncogenesis in transgenic mice. Oncogene 1997; 14: 395–404. DOI: 10.1038/sj.onc.1200850
6. Colnot S, Decaens T, Niwa-Kawakita M, Godard C, Hamard G, Kahn A et al. Liver-targeted disruption of Apc in mice activates beta-catenin signaling and leads to hepatocellular carcinomas. Proc Natl Acad Sci USA 2004; 101: 17216–17221. DOI: 10.1073/pnas.0404761101
7. Pylayeva-Gupta Y, Grabocka E, Bar-Sagi D. Ras oncogenes: weaving a tumorigenic web. Nat Rev Cancer 2011; 11: 761–774. DOI: 10.1038/nrc3106
8. Karnoub AE, Weinberg RA. RAS oncogenes: split personalities. Nat Rev Mol Cell Biol 2008; 9: 517–531. DOI: 10.1038/nrm2438
9. Calvisi DF, Ladu S, Gorden A, Farina M, Conner EA, Lee JS et al. Ubiquitous activation of Ras and Jak/Stat pathways in human HCC. Gastroenterology 2006; 130: 1117–1128. DOI: 10.1053/j.gastro.2006.01.006
10. Fan R, Chen P, Zhao D, Tong JL, Li J, Liu F. Cooperation of deregulated Notch signaling and Ras pathway in human hepatocarcinogenesis. J Mol Histol 2011; 42: 473–481. DOI: 10.1007/s10735-011-9353-3
11. Keng VW, Tschida BR, Bell JB, Largaespada DA. Modeling hepatitis B virus X-induced hepatocellular carcinoma in mice with the Sleeping Beauty transposon system. Hepatology 2011; 53: 781–790. DOI: 10.1002/hep.24091
12. Harada N, Oshima H, Katoh M, Tamai Y, Oshima M, Taketo MM. Hepatocarcinogenesis in mice with beta-catenin and Ha-ras gene mutations. Cancer Res 2004; 64: 48–54. DOI: 10.1158/0008-5472.CAN-03-2123
13. O'Dell MR, Huang JL, Whitney-Miller CL, Deshpande V, Rothberg P, Grose V et al. Kras(G12D) and p53 mutation cause primary intrahepatic cholangiocarcinoma. Cancer Res 2012; 72: 1557–1567. DOI: 10.1158/0008-5472.CAN-11-3596
14. Tuveson DA, Zhu L, Gopinathan A, Willis NA, Kachatrian L, Grochow R et al. Mist1-KrasG12D knock-in mice develop mixed differentiation metastatic exocrine pancreatic carcinoma and hepatocellular carcinoma. Cancer Res 2006; 66: 242–247. DOI: 10.1158/0008-5472.CAN-05-2305
15. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 2012; 142: 1264–1273 e1261. DOI: 10.1053/j.gastro.2011.12.061
16. Li Y, Tang ZY, Hou JX. Hepatocellular carcinoma: insight from animal models. Nat Rev Gastroenterol Hepatol 2012; 9: 32–43. DOI: 10.1038/nrgastro.2011.196
17. Tang H, Oishi N, Kaneko S, Murakami S. Molecular functions and biological roles of hepatitis B virus x protein. Cancer Sci 2006; 97: 977–983. DOI: 10.1111/j.1349-7006.2006.00299.x
18. Bock CT, Toan NL, Koeberlein B, Song le H, Chin R, Zentgraf H et al. Subcellular mislocalization of mutant hepatitis B X proteins contributes to modulation of STAT/SOCS signaling in hepatocellular carcinoma. Intervirology 2008; 51: 432–443. DOI: 10.1159/000209672
19. Cha MY, Kim CM, Park YM, Ryu WS. Hepatitis B virus X protein is essential for the activation of Wnt/beta-catenin signaling in hepatoma cells. Hepatology 2004; 39: 1683–1693. DOI: 10.1002/hep.20245
20. Zhang X, Zhang H, Ye L. Effects of hepatitis B virus X protein on the development of liver cancer. J Lab Clin Med 2006; 147: 58–66. DOI: 10.1016/j.lab.2005.10.003
21. Wang Y, Cui F, Lv Y, Li C, Xu X, Deng C et al. HBsAg and HBx knocked into the p21 locus causes hepatocellular carcinoma in mice. Hepatology 2004; 39: 318–324. DOI: 10.1002/hep.20076
22. Cui F, Wang Y, Wang J, Wei K, Hu J, Liu F et al. The up-regulation of proteasome subunits and lysosomal proteases in hepatocellular carcinomas of the HBx gene knockin transgenic mice. Proteomics 2006; 6: 498–504. DOI: 10.1002/pmic.200500218
23. Sun Q, Wang Y, Zhang Y, Liu F, Cheng X, Hou N et al. Expression profiling reveals dysregulation of cellular cytoskeletal genes in HBx-induced hepatocarcinogenesis. Cancer Biol Ther 2007; 6: 668–674. DOI: 10.4161/cbt.6.5.3955
24. Sun Q, Zhang Y, Liu F, Zhao X, Yang X. Identification of candidate biomarkers for hepatocellular carcinoma through pre-cancerous expression analysis in an HBx transgenic mouse. Cancer Biol Ther 2007; 6: 1532–1538. DOI: 10.4161/cbt.6.10.4683
25. Longato L, de la Monte S, Kuzushita N, Horimoto M, Rogers AB, Slagle BL et al. Overexpression of insulin receptor substrate-1 and hepatitis Bx genes causes premalignant alterations in the liver. Hepatology 2009; 49: 1935–1943. DOI: 10.1002/hep.22856
26. Jackson EL, Willis N, Mercer K, Bronson RT, Crowley D, Montoya R et al. Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev 2001; 15: 3243–3248. DOI: 10.1101/gad.943001
27. Postic C, Shiota M, Niswender KD, Jetton TL, Chen Y, Moates JM et al. Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic beta cell-specific gene knock-outs using Cre recombinase. J Biol Chem 1999; 274: 305–315. DOI: 10.1074/jbc.274.1.305
28. Kim YC, Song KS, Yoon G, Nam MJ, Ryu WS. Activated ras oncogene collaborates with HBx gene of hepatitis B virus to transform cells by suppressing HBx-mediated apoptosis. Oncogene 2001; 20: 16–23. DOI: 10.1038/sj.onc.1203840
29. Oishi N, Shilagardi K, Nakamoto Y, Honda M, Kaneko S, Murakami S. Hepatitis B virus X protein overcomes oncogenic RAS-induced senescence in human immortalized cells. Cancer Sci 2007; 98: 1540–1548. DOI: 10.1111/j.1349-7006.2007.00579.x
30. Schmitz KJ, Wohlschlaeger J, Lang H, Sotiropoulos GC, Malago M, Steveling K et al. Activation of the ERK and AKT signalling pathway predicts poor prognosis in hepatocellular carcinoma and ERK activation in cancer tissue is associated with hepatitis C virus infection. J Hepatol 2008; 48: 83–90. DOI: 10.1016/j.jhep.2007.08.018
31. Wang SN, Lee KT, Tsai CJ, Chen YJ, Yeh YT. Phosphorylated p38 and JNK MAPK proteins in hepatocellular carcinoma. Eur J Clin Invest 2012; 42: 1295–1301. DOI: 10.1111/eci.12003
32. Yang SF, Wang SN, Wu CF, Yeh YT, Chai CY, Chunag SC et al. Altered p-STAT3 (tyr705) expression is associated with histological grading and intratumour microvessel density in hepatocellular carcinoma. J Clin Pathol 2007; 60: 642–648. DOI: 10.1136/jcp.2006.036970
33. Benn J, Schneider RJ. Hepatitis B virus HBx protein activates Ras-GTP complex formation and establishes a Ras, Raf, MAP kinase signaling cascade. Proc Natl Acad Sci USA 1994; 91: 10350–10354. DOI: 10.1073/pnas.91.22.10350
34. Lee YI, Kang-Park S, Do SI. The hepatitis B virus-X protein activates a phosphatidylinositol 3-kinase-dependent survival signaling cascade. J Biol Chem 2001; 276: 16969–16977. DOI: 10.1074/jbc.M011263200
35. Xia L, Tian D, Huang W, Zhu H, Wang J, Zhang Y et al. Upregulation of IL-23 expression in patients with chronic hepatitis B is mediated by the HBx/ERK/NF-kappaB pathway. J Immunol 2012; 188: 753–764. DOI: 10.4049/jimmunol.1101652
36. Tarn C, Zou L, Hullinger RL, Andrisani OM. Hepatitis B virus X protein activates the p38 mitogen-activated protein kinase pathway in dedifferentiated hepatocytes. J Virol 2002; 76: 9763–9772. DOI: 10.1128/JVI.76.19.9763-9772.2002
37. Lee SG, Rho HM. Transcriptional repression of the human p53 gene by hepatitis B viral X protein. Oncogene 2000; 19: 468–471. DOI: 10.1038/sj.onc.1203312
38. Nishida N, Fukuda Y, Ishizaki K. Molecular aspects of hepatocarcinogenesis and their clinical implications - review. Int J Oncol 1994; 4: 615–622.
39. Hsieh A, Kim HS, Lim SO, Yu DY, Jung G. Hepatitis B viral X protein interacts with tumor suppressor adenomatous polyposis coli to activate Wnt/beta-catenin signaling. Cancer Lett 2011; 300: 162–172. DOI: 10.1016/j.canlet.2010.09.018
40. Lara-Pezzi E, Serrador JM, Montoya MC, Zamora D, Yanez-Mo M, Carretero M et al. The hepatitis B virus X protein (HBx) induces a migratory phenotype in a CD44-dependent manner: possible role of HBx in invasion and metastasis. Hepatology 2001; 33: 1270–1281. DOI: 10.1053/jhep.2001.1270
41. Kim HR, Lee SH, Jung G. The hepatitis B viral X protein activates NF-kappaB signaling pathway through the up-regulation of TBK1. FEBS Lett 2010; 584: 525–530. DOI: 10.1016/j.febslet.2009.11.091
42. Liu J, Lian Z, Han S, Waye MM, Wang H, Wu MC et al. Downregulation of E-cadherin by hepatitis B virus X antigen in hepatocellullar carcinoma. Oncogene 2006; 25: 1008–1017. DOI: 10.1038/sj.onc.1209138
43. Chappell WH, Steelman LS, Long JM, Kempf RC, Abrams SL, Franklin RA et al. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: rationale and importance to inhibiting these pathways in human health. Oncotarget 2011; 2: 135–164. DOI: 10.18632/oncotarget.240
44. Macnee W, Allan RJ, Jones I, De Salvo MC, Tan LF. Efficacy and safety of the oral p38 inhibitor PH-797804 in chronic obstructive pulmonary disease: a randomised clinical trial. Thorax 2013; 68: 738–745. DOI: 10.1136/thoraxjnl-2012-202744
45. Miyoshi K, Takaishi M, Nakajima K, Ikeda M, Kanda T, Tarutani M et al. Stat3 as a therapeutic target for the treatment of psoriasis: a clinical feasibility study with STA-21, a Stat3 inhibitor. J Invest Dermatol 2011; 131: 108–117. DOI: 10.1038/jid.2010.255