Downregulation of γ-catenin inhibits CML cell growth and potentiates the response of CML cells to imatinib through β-catenin inhibition

  • Authors:
    • Chang-Chun Niu
    • Chen Zhao
    • Zhen-Dong Yang
    • Xiao-Li Zhang
    • Wei-Ru Wu
    • Jing Pan
    • Zhi-Qiang Li
    • Wei Ding
    • Zhong Yang
    • Wei-Ke Si
  • View Affiliations

  • Published online on: December 6, 2012     https://doi.org/10.3892/ijmm.2012.1207
  • Pages: 453-458
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Abstract

γ-catenin plays different roles in different types of tumors, and its role in chronic myeloid leukemia (CML) cells has yet to be identified. In our study, two CML cell lines (K562, KU812) had higher γ-catenin expression levels compared to five types of BCR-ABL-negative leukemia cells. Knockdown of the expression of BCR-ABL resulted in downregulation of γ-catenin. Furthermore, downregulation of γ-catenin by siRNA inhibited the proliferation and colony formation of CML cells and the expression of the c-Myc and cyclin D1 genes; downregulation of γ-catenin also potentiated the effects of imatinib (inhibiting CML cell proliferation and inducing apoptosis) and suppressed the anti-apoptotic genes Bcl-xL and survivin. We also showed that downregulation of γ-catenin suppressed the phosphorylation of STAT5, promoted the phosphorylation of β-catenin and reduced the translocation of β-catenin into the nucleus, although there were no effects on the total level of β-catenin expression in the whole cells. Furthermore, downregulation of γ-catenin was found to promote glycogen synthase kinase-3β (GSK3β) and inhibit its phosphorylation. Collectively, our results suggest that γ-catenin is an oncogene protein in CML that can be regulated by BCR-ABL and that suppression of γ-catenin inhibits CML cell growth and potentiates the effects of imatinib on CML cells through inhibition of the activation of STAT5 and suppression of β-catenin by activating GSK3β.
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February 2013
Volume 31 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Niu C, Zhao C, Yang Z, Zhang X, Wu W, Pan J, Li Z, Ding W, Yang Z, Si W, Si W, et al: Downregulation of γ-catenin inhibits CML cell growth and potentiates the response of CML cells to imatinib through β-catenin inhibition. Int J Mol Med 31: 453-458, 2013
APA
Niu, C., Zhao, C., Yang, Z., Zhang, X., Wu, W., Pan, J. ... Si, W. (2013). Downregulation of γ-catenin inhibits CML cell growth and potentiates the response of CML cells to imatinib through β-catenin inhibition. International Journal of Molecular Medicine, 31, 453-458. https://doi.org/10.3892/ijmm.2012.1207
MLA
Niu, C., Zhao, C., Yang, Z., Zhang, X., Wu, W., Pan, J., Li, Z., Ding, W., Yang, Z., Si, W."Downregulation of γ-catenin inhibits CML cell growth and potentiates the response of CML cells to imatinib through β-catenin inhibition". International Journal of Molecular Medicine 31.2 (2013): 453-458.
Chicago
Niu, C., Zhao, C., Yang, Z., Zhang, X., Wu, W., Pan, J., Li, Z., Ding, W., Yang, Z., Si, W."Downregulation of γ-catenin inhibits CML cell growth and potentiates the response of CML cells to imatinib through β-catenin inhibition". International Journal of Molecular Medicine 31, no. 2 (2013): 453-458. https://doi.org/10.3892/ijmm.2012.1207