Send to

Choose Destination
See comment in PubMed Commons below
Clin Cancer Res. 2005 Jun 15;11(12):4295-304.

Elevated expression of Wnt antagonists is a common event in hepatoblastomas.

Author information

Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany.


Hepatoblastomas are the most frequent malignant liver tumors of childhood. A high frequency of activating beta-catenin mutations in hepatoblastomas indicates that the Wnt signaling pathway plays an important role in the development of this embryonic neoplasm. Stabilization of beta-catenin leads to an increased formation of nuclear beta-catenin-T-cell factor complexes and altered expression of Wnt-inducible target genes. In this study, we analyzed the mRNA expression levels of nine Wnt genes, including c-JUN, c-MYC, CYCLIN D1, FRA-1, NKD-1, ITF-2, MMP-7, uPAR, and beta-TRCP, by competitive reverse transcription-PCR. We analyzed 23 hepatoblastoma biopsies for which matching liver tissue was available, 6 hepatoblastoma cell lines, and 3 human fetal liver samples. beta-TRCP and NKD-1 were highly expressed in all hepatoblastoma samples, independent of the beta-catenin mutational status, in comparison with their nontumorous counterparts. beta-TRCP mRNA overexpression was associated with accumulation of intracytoplasmic and nuclear beta-TrCP protein. In human liver tumor cells without beta-catenin mutations, Nkd-1 inhibited the Wnt-3a-activated Tcf-responsive-luciferase reporter activity, whereas Nkd-1 in hepatoblastomas with beta-catenin mutations had no antagonistic effect. Our data emphasize the inhibitory effect of beta-TrCP and Nkd-1 on the Wnt signaling pathway in a manner analogous to Conductin (AXIN2) and Dkk-1, inhibitors shown previously to be up-regulated in hepatoblastomas. Our findings indicate that overexpression of the Wnt antagonists Nkd-1 and beta-TrCP reveals an activation of the Wnt signaling pathway as a common event in hepatoblastomas. We propose that Nkd-1 and beta-TrCP may be used as possible diagnostic markers for the activated Wnt signaling pathway in hepatoblastomas.

[Indexed for MEDLINE]
Free full text

Publication type, MeSH terms, Substances

Publication type

MeSH terms


PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center