Skip to main content

Advertisement

SpringerLink
Log in

β-Catenin overexpression in malignant glioma and its role in proliferation and apoptosis in glioblastma cells

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

β-Catenin, a core component of Wnt/β-catenin signaling, has been shown to be a crucial factor in a broad range of tumors, while its role in glioma is not well understood. In this study, the expression of β-catenin in astrocytic glioma tissues with different grade and human normal cerebral tissues was examined using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. We found a higher expression level of β-catenin in astrocytic glioma patients with high grade in comparison with the normal controls. Additionally, siRNA was transfected into human U251 glioblastoma cells by liposome after the design of siRNA was confirmed to effectively inhibit the expression of β-catenin by RT-PCR. Compared to the control siRNA group, siRNA-mediated knockdown of β-catenin in human U251 cells inhibited cell proliferation, resulted in cell apoptosis, and arrested cell cycle in G 0/G 1. Additionally, downregulation of β-catenin decreased the expression level of cyclin D1, c-Myc and c-jun. Taken together, these results indicate that overexpression of β-catenin may be an important contributing factor to glioma progression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Peifer M, Polakis P. Wnt signaling in oncogenesis and embryogenesis-a look outside the nucleus. Science. 2000;287:1606–9.

    Article  PubMed  CAS  Google Scholar 

  2. Fodde R, Brabletz T. Wnt/beta-catenin signaling in cancer stemness and malignant behavior. Curr Opin Cell Biol. 2007;19:150–8.

    Article  PubMed  CAS  Google Scholar 

  3. Polakis P. Wnt signaling and cancer. Genes Dev. 2000;14:1837–51.

    PubMed  CAS  Google Scholar 

  4. Barker N. The canonical Wnt/beta-catenin signalling pathway. Methods Mol Biol. 2008;468:5–15.

    Article  PubMed  CAS  Google Scholar 

  5. Simon M, Grandage VL, Linch DC, Khwaja A. Constitutive activation of the Wnt/beta-catenin signalling pathway in acute myeloid leukaemia. Oncogene. 2005;24:2410–20.

    Article  PubMed  CAS  Google Scholar 

  6. Gavert N, Ben-Ze’ev A. Beta-catenin signaling in biological control and cancer. J Cell Biochem. 2007;102:820–8.

    Article  PubMed  CAS  Google Scholar 

  7. Dihlmann S, von Knebel Doeberitz M. Wnt/beta-catenin-pathway as a molecular target for future anti-cancer therapeutics. Int J Cancer. 2005;113:515–24.

    Article  PubMed  CAS  Google Scholar 

  8. Karim R, Tse G, Putti T, Scolyer R, Lee S. The significance of the Wnt pathway in the pathology of human cancers. Pathology. 2004;36:120–8.

    Article  PubMed  CAS  Google Scholar 

  9. Hatsell S, Rowlands T, Hiremath M, Cowin P. Beta-catenin and Tcfs in mammary development and cancer. J Mammary Gland Biol Neoplasia. 2003;8:145–58.

    Article  PubMed  Google Scholar 

  10. Mann B, et al. Target genes of β-catenin-T cell-factor/lymphoidenhancer-factor signaling in human colorectal carcinomas. Proc Natl Acad Sci USA. 1999;96:1603–8.

    Article  PubMed  CAS  Google Scholar 

  11. Rowlands TM, Pechenkina IV, Hatsell S, Cowin P. Beta-catenin and cyclin D1: connecting development to breast cancer. Cell Cycle. 2004;3:145–8.

    Article  PubMed  CAS  Google Scholar 

  12. Pu P, et al. Downregulation of Wnt2 and beta-catenin by siRNA suppresses malignant glioma cell growth. Cancer Gene Ther. 2009;16:351–61.

    Article  PubMed  CAS  Google Scholar 

  13. Sareddy GR, Panigrahi M, Challa S, Mahadevan A, Babu PP. Activation of Wnt/beta-catenin/Tcf signaling pathway in human astrocytomas. Neurochem Int. 2009;55:307–17.

    Article  PubMed  CAS  Google Scholar 

  14. Liu X, et al. Overexpression of an isoform of AML1 in acute leukemia and its potential role in leukemogenesis. Leukemia. 2009;23:739–45.

    Article  PubMed  CAS  Google Scholar 

  15. Elbashir SM, Harborth J, Weber K, Tuschl T. Analysis of gene function in somatic mammalian cells using a small interference RNAs. Methods. 2002;26:199–213.

    Article  PubMed  CAS  Google Scholar 

  16. Müller T, Choidas A, Reichmann E, Ullrich A. Phosphorylation and free pool of beta-catenin are regulated by tyrosine kinases and tyrosine phosphatases during epithelial cell migration. J Biol Chem. 1999;274:10173–83.

    Article  PubMed  Google Scholar 

  17. Utsuki S, et al. Relationship between the expression of E-, N-cadherins and beta-catenin and tumor grade in astrocytomas. J Neurooncol. 2002;57:187–92.

    Article  PubMed  Google Scholar 

  18. Sareddy GR, Challa S, Panigrahi M, Babu PP. Wnt/beta-catenin/Tcf signaling pathway activation in malignant progression of rat gliomas induced by transplacental N-ethyl-N-nitrosourea exposure. Neurochem Res. 2009;34:1278–88.

    Article  PubMed  CAS  Google Scholar 

  19. Kim JK, Diehl JA. Nuclear cyclin D1: an oncogenic driver in human cancer. J Cell Physiol. 2009;220:292–6.

    Article  PubMed  CAS  Google Scholar 

  20. Dang CV, et al. The c-Myc target gene network. Semin Cancer Biol. 2006;16:253–64.

    Article  PubMed  CAS  Google Scholar 

  21. Saadeddin A, Babaei-Jadidi R, Spencer-Dene B, Nateri AS. The links between transcription, beta-catenin/JNK signaling, and carcinogenesis. Mol Cancer Res. 2009;7:1189–96.

    Article  PubMed  CAS  Google Scholar 

  22. Takayama S, Rogatsky I, Schwarcz LE, Darimont BD. The glucocorticoid receptor represses cyclin D1 by targeting the TCF/beta-catenin complex. J Biol Chem. 2006;281:17856–63.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We are grateful to Prof. Qing Rao and Prof. Min Wang (Institute of Hematology and Blood Disease Hospital, China) for technical support. This work was supported by Postdoctoral Science Found (20080440423) of China and Clinical and Basic Cooperation Fund of Capital University of Medical Sciences (2006JL36).

Author information

Authors and Affiliations

  1. Cerebrovascular Diseases Research Institute, Key Laboratory of Neurodegenerative Diseases of Ministry of Education and Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 100053, Beijing, People’s Republic of China

    Xiangrong Liu, Xunming Ji, Yumin Luo & Feng Ling

  2. Department of Neurosurgery, Beijing Tiantan Hospital, Capital University of Medical Sciences, 100050, Beijing, People’s Republic of China

    Lei Wang

  3. Department of Neurosurgery, Beijing Tongren Hospital, Capital University of Medical Sciences, 100730, Beijing, People’s Republic of China

    Shangfeng Zhao

Authors
  1. Xiangrong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shangfeng Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xunming Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yumin Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Feng Ling
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Feng Ling.

Additional information

Xiangrong Liu and Lei Wang contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, X., Wang, L., Zhao, S. et al. β-Catenin overexpression in malignant glioma and its role in proliferation and apoptosis in glioblastma cells. Med Oncol 28, 608–614 (2011). https://doi.org/10.1007/s12032-010-9476-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-010-9476-5

Keywords

Search

Navigation