Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
May 2013 Volume 42 Issue 5

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
May 2013 Volume 42 Issue 5

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

The hepatitis B virus X protein downregulates NF-κB signaling pathways through decreasing the Notch signaling pathway in HBx-transformed L02 cells

  • Authors:
    • Jing Luo
    • Haiyan Zhou
    • Fan Wang
    • Xiumei Xia
    • Qian Sun
    • Ronghua Wang
    • Bin Cheng
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
  • Pages: 1636-1643
    |
    Published online on: February 27, 2013
       https://doi.org/10.3892/ijo.2013.1842
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Hepatitis B virus X protein (HBx) is implicated in the pathogenesis of hepatocellular carcinoma, which has been found to be associated with Notch and NF-κB signaling. This study aimed to investigate the crosstalk between Notch and NF-κB pathways in HBx-related hepatocellular carcinoma. An HBx-transformed non-tumor hepatic cell line L02 (L02/HBx) was previously established. Immunofluorescence assays were performed to visualize HBx and the Notch intracellular domain (NICD) in cell nuclei. Co-immunoprecipitation assays were used to investigate physical interactions between HBx and components of the Notch signaling pathway (NICD and JAG1), NF-κB signaling pathway (p65 and p50) or IκBα. L02/HBx cells were treated with the Notch signal inhibitor DAPT or Notch1 siRNA to inhibit the Notch1 pathway. qRT-PCR was used to quantify the expression of the p65, p50 and IκBα genes. Protein expression changes in cytoplasm and nuclei after treatment with DAPT or Notch1 siRNA were analyzed by western blotting and EMSA assays. We found that HBx directly regulated Notch1 signaling, which cross-talked with the NF-κB pathway. Downregulation of Notch1 decreased the binding of NF-κB p65 to its target gene promoter, reduced NF-κB expression and enhanced IκBα expression. The results suggest that HBx functions through the Notch signaling pathway; Notch contributes to hepatocarcinogenesis partially by regulating the NF-κB pathway. Our findings provide new insights into the role of Notch and NF-κB signaling in the progression of hepatocellular carcinoma related to HBx.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1. 

Jemal A, Bray F, Melissa M, et al: Global Cancer Statistics. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar

2. 

Hashem BE and Rudolph KL: Hepatocellular carcinoma epidemiology and molecular carcinogenesis. Gastroenterology. 132:2557–2576. 2007. View Article : Google Scholar

3. 

Feitelson MA and Duan LX: Hepatitis B virus X antigen in the pathogenesis of chronic infections and the development of hepatocellular carcinoma. Am J Pathol. 150:1141–1157. 1997.PubMed/NCBI

4. 

Wang F, Zhou H, Xia X, et al: Activated Notch signaling is required for hepatitis B virus X protein to promote proliferation and survival of human hepatic cells. Cancer Lett. 298:64–73. 2010. View Article : Google Scholar : PubMed/NCBI

5. 

Lai EC: Notch signaling: control of cell communication and cell fate. Development. 131:965–973. 2004. View Article : Google Scholar : PubMed/NCBI

6. 

Miele L: Notch signaling. Clin Cancer Res. 12:1074–1079. 2006. View Article : Google Scholar : PubMed/NCBI

7. 

Miele L, Golde T and Osborne B: Notch signaling in cancer. Curr Mol Med. 6:905–918. 2006. View Article : Google Scholar : PubMed/NCBI

8. 

Kopan R and Ilagan MX: Gamma-secretase: proteasome of the membrane? Nat Rev Mol Cell Biol. 5:499–504. 2004. View Article : Google Scholar : PubMed/NCBI

9. 

Berman JN and Look AT: Targeting transcription factors in acute leukemia in children. Curr Drug Targets. 8:727–737. 2007. View Article : Google Scholar : PubMed/NCBI

10. 

Rangarajan A, Talora C, Okuyama R, et al: Notch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation. EMBO J. 20:3427–3436. 2001. View Article : Google Scholar : PubMed/NCBI

11. 

Ronchini C and Capobianco AJ: Induction of cyclin D1 transcription and CDK2 activity by Notch(ic): implication for cell cycle disruption in transformation by Notch(ic). Mol Cell Biol. 1:5925–5934. 2001. View Article : Google Scholar : PubMed/NCBI

12. 

Baonza A and Freeman M: Control of cell proliferation in the Drosophila eye by Notch signaling. Dev Cell. 8:529–539. 2005. View Article : Google Scholar : PubMed/NCBI

13. 

Cheng P, Zlobin A, Volgina V, et al: Notch-1 regulates NF-kappaB activity in hemopoietic progenitor cells. J Immunol. 167:4458–4467. 2001. View Article : Google Scholar : PubMed/NCBI

14. 

Klinakis A, Szabolcs M, Politi K, et al: Myc is a Notch1 transcriptional target and a requisite for Notch1-induced mammary tumorigenesis in mice. Proc Natl Acad Sci USA. 103:9262–9267. 2006. View Article : Google Scholar : PubMed/NCBI

15. 

Diao J, Garces R and Richardson CD: X protein of hepatitis B virus modulates cytokine and growth factor related signal transduction pathways during the course of viral infections and hepatocarcinogenesis. Cytokine Growth Factor Rev. 12:189–205. 2001. View Article : Google Scholar

16. 

Seto E, Mitchell PJ and Yen TS: Transactivation by the hepatitis B virus X protein depends on AP-2 and other transcription factors. Nature. 344:72–74. 1990. View Article : Google Scholar : PubMed/NCBI

17. 

Lucito R and Schneider RJ: Hepatitis B virus X protein activates transcription factor NF-kappa B without a requirement for protein kinase C. J Virol. 66:983–991. 1992.PubMed/NCBI

18. 

Meyer M, Caselmann WH, Schluter V, et al: Hepatitis B virus transactivator MHBst: activation of NF-kappa B, selective inhibition by antioxidants and integral membrane localization. EMBO J. 11:2991–3001. 1992.PubMed/NCBI

19. 

Campbell KJ and Perkins ND: Regulation of NF-kappaB function. Biochem Soc Symp. 73:165–180. 2006.

20. 

Perkins ND: Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol. 8:49–62. 2007. View Article : Google Scholar : PubMed/NCBI

21. 

Maniati E, Bossard M, Cook N, et al: Crosstalk between the canonical NF-κB and Notch signaling pathways inhibits PPARγ expression and promotes pancreatic cancer progression in mice. J Clin Invest. 121:4685–4699. 2011.

22. 

Pan H, Zhou W, He W, et al: Genistein inhibits MDA-MB-231 triple-negative breast cancer cell growth by inhibiting NF-κB activity via the Notch-1 pathway. Int J Mol Med. 30:337–343. 2012.PubMed/NCBI

23. 

Schwarzer R, Dörken B and Jundt F: Notch is an essential upstream regulator of NF-κB and is relevant for survival of Hodgkin and Reed-Sternberg cells. Leukemia. 26:806–813. 2012.PubMed/NCBI

24. 

Cheng B, Zheng Y, Guo XR, et al: Hepatitis B viral X protein alters the biological features and expressions of DNA repair enzymes in LO2 cells. Liver Int. 30:319–326. 2010. View Article : Google Scholar : PubMed/NCBI

25. 

Wang Z, Banerjee S, Ahmad A, et al: Activated K-ras and INK4a/Arf deficiency cooperate during the development of pancreatic cancer by activation of Notch and NF-κB signaling pathways. PLoS One. 6:e205372011.PubMed/NCBI

26. 

Berasain C, Castillo J, Perugorria MJ, et al: Infammation and liver cancer: new molecular links. Ann NY Acad Sci. 1155:206–221. 2009. View Article : Google Scholar : PubMed/NCBI

27. 

Lupberger J and Hildt E: Hepatitis B virus-induced concogenesis. World J Gastroenterol. 13:74–81. 2007. View Article : Google Scholar : PubMed/NCBI

28. 

Qiao L, Zhang H, Yu J, et al: Constitutive activation of NF-kappaB in human hepatocellular carcinoma: evidence of a cytoprotective role. Hum Gene Ther. 17:280–290. 2006. View Article : Google Scholar : PubMed/NCBI

29. 

Gao J, Chen C, Hong L, et al: Expression of Jagged1 and its association with hepatitis B virus X protein in hepatocellular carcinoma. Biochem Biophys Res Commun. 356:341–347. 2007. View Article : Google Scholar : PubMed/NCBI

30. 

Karin M: NF-kappaB and cancer: mechanisms and targets. Mol Carcinog. 45:355–361. 2006. View Article : Google Scholar : PubMed/NCBI

31. 

Luedde T and Schwabe RF: NF-κB in the liver - linking injury, fibrosis and hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 8:108–118. 2011.

32. 

Beg AA and Baldwin JR: The I kappa B proteins: multifunctional regulators of Rel/NF-kappa B transcription factors. Genes Dev. 7:2064–2070. 1993. View Article : Google Scholar : PubMed/NCBI

33. 

Oakley F, Mann J, Ruddell RG, et al: Basal expression of IkappaBalpha is controlled by the mammalian transcriptional repressor RBP-J (CBF1) and its activator Notch1. J Biol Chem. 278:24359–24370. 2003. View Article : Google Scholar : PubMed/NCBI

34. 

Monsalve E, Ruiz-García A, Baladrón V, et al: Notch1 upregulates LPS-induced macrophage activation by increasing NF-kappaB activity. Eur J Immunol. 39:2556–2570. 2009. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Luo J, Zhou H, Wang F, Xia X, Sun Q, Wang R and Cheng B: The hepatitis B virus X protein downregulates NF-κB signaling pathways through decreasing the Notch signaling pathway in HBx-transformed L02 cells. Int J Oncol 42: 1636-1643, 2013.
APA
Luo, J., Zhou, H., Wang, F., Xia, X., Sun, Q., Wang, R., & Cheng, B. (2013). The hepatitis B virus X protein downregulates NF-κB signaling pathways through decreasing the Notch signaling pathway in HBx-transformed L02 cells. International Journal of Oncology, 42, 1636-1643. https://doi.org/10.3892/ijo.2013.1842
MLA
Luo, J., Zhou, H., Wang, F., Xia, X., Sun, Q., Wang, R., Cheng, B."The hepatitis B virus X protein downregulates NF-κB signaling pathways through decreasing the Notch signaling pathway in HBx-transformed L02 cells". International Journal of Oncology 42.5 (2013): 1636-1643.
Chicago
Luo, J., Zhou, H., Wang, F., Xia, X., Sun, Q., Wang, R., Cheng, B."The hepatitis B virus X protein downregulates NF-κB signaling pathways through decreasing the Notch signaling pathway in HBx-transformed L02 cells". International Journal of Oncology 42, no. 5 (2013): 1636-1643. https://doi.org/10.3892/ijo.2013.1842
Copy and paste a formatted citation
x
Spandidos Publications style
Luo J, Zhou H, Wang F, Xia X, Sun Q, Wang R and Cheng B: The hepatitis B virus X protein downregulates NF-κB signaling pathways through decreasing the Notch signaling pathway in HBx-transformed L02 cells. Int J Oncol 42: 1636-1643, 2013.
APA
Luo, J., Zhou, H., Wang, F., Xia, X., Sun, Q., Wang, R., & Cheng, B. (2013). The hepatitis B virus X protein downregulates NF-κB signaling pathways through decreasing the Notch signaling pathway in HBx-transformed L02 cells. International Journal of Oncology, 42, 1636-1643. https://doi.org/10.3892/ijo.2013.1842
MLA
Luo, J., Zhou, H., Wang, F., Xia, X., Sun, Q., Wang, R., Cheng, B."The hepatitis B virus X protein downregulates NF-κB signaling pathways through decreasing the Notch signaling pathway in HBx-transformed L02 cells". International Journal of Oncology 42.5 (2013): 1636-1643.
Chicago
Luo, J., Zhou, H., Wang, F., Xia, X., Sun, Q., Wang, R., Cheng, B."The hepatitis B virus X protein downregulates NF-κB signaling pathways through decreasing the Notch signaling pathway in HBx-transformed L02 cells". International Journal of Oncology 42, no. 5 (2013): 1636-1643. https://doi.org/10.3892/ijo.2013.1842
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team