In vitro RNA interference against β-catenin inhibits the proliferation of pediatric hepatic tumors

  • Authors:
    • Surasak Sangkhathat
    • Takeshi Kusafuka
    • Jiangyong Miao
    • Akihiro Yoneda
    • Keigo Nara
    • Seiji Yamamoto
    • Yasafumi Kaneda
    • Masahiro Fukuzawa
  • View Affiliations

  • Published online on: March 1, 2006     https://doi.org/10.3892/ijo.28.3.715
  • Pages: 715-722
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Abstract

Mutations of β-catenin have been identified in the majority of pediatric hepatic malignancies, including hepatoblastoma (HB) and hepatocellular carcinoma (HCC), suggesting its important contribution in hepatic tumorigenesis in this age group. However, the role of β-catenin/canonical Wnt signaling pathway in the neoplastic growth of cancer cells has not been directly studied. To address β-catenin's capability in maintaining the malignant phenotype in established pediatric HB and HCC cell lines, HuH-6 and HepG2, harboring mutated and overexpressed β-catenin, we carried out a series of in vitro analyses through a transfection of short interfering RNAs (siRNAs) to generate a loss-of-function model. HuH-7, another HB cell line derived from a pediatric patient without a stabilizing mutation was used for comparison. RNA interference successfully manipulated the degradation of overexpressed β-catenin. In all cell lines, β-catenin mRNA was suppressed by 80-90% after 48 h of transfection, and a reduction of its protein expression was demonstrated. In HuH-6 and HepG2, the pre-existing β-catenin nuclear accumulation disappeared and reductions of β-catenin downstream target genes, c-myc and cyclinD1, were also evidenced after the treatment. The in vitro proliferation of both cell lines was transiently inhibited. In contrast, the suppression of β-catenin in HuH-7 did not lead to a significant change in the expression of target genes or cellular proliferation. Our data indicate that β-catenin can be considered a specific target for gene therapy in pediatric hepatic tumors with mutations and overexpression of this gene.

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March 2006
Volume 28 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Sangkhathat S, Kusafuka T, Miao J, Yoneda A, Nara K, Yamamoto S, Kaneda Y and Fukuzawa M: In vitro RNA interference against β-catenin inhibits the proliferation of pediatric hepatic tumors. Int J Oncol 28: 715-722, 2006
APA
Sangkhathat, S., Kusafuka, T., Miao, J., Yoneda, A., Nara, K., Yamamoto, S. ... Fukuzawa, M. (2006). In vitro RNA interference against β-catenin inhibits the proliferation of pediatric hepatic tumors. International Journal of Oncology, 28, 715-722. https://doi.org/10.3892/ijo.28.3.715
MLA
Sangkhathat, S., Kusafuka, T., Miao, J., Yoneda, A., Nara, K., Yamamoto, S., Kaneda, Y., Fukuzawa, M."In vitro RNA interference against β-catenin inhibits the proliferation of pediatric hepatic tumors". International Journal of Oncology 28.3 (2006): 715-722.
Chicago
Sangkhathat, S., Kusafuka, T., Miao, J., Yoneda, A., Nara, K., Yamamoto, S., Kaneda, Y., Fukuzawa, M."In vitro RNA interference against β-catenin inhibits the proliferation of pediatric hepatic tumors". International Journal of Oncology 28, no. 3 (2006): 715-722. https://doi.org/10.3892/ijo.28.3.715