Please use this identifier to cite or link to this item:
Title: HGF/c-Met related activation of β-catenin in hepatoblastoma
Authors: Purcell, R.
Childs, Margaret
Maibach, R.
Miles, C.
Turner, C.
Zimmermann, A.
Sullivan, M.
First Published: 12-Oct-2011
Publisher: BioMed Central Ltd
Citation: Journal of Experimental & Clinical Cancer Research, 2011, 30 : 96
Abstract: Background: Activation of beta-catenin is a hallmark of hepatoblastoma (HB) and appears to play a crucial role in its pathogenesis. While aberrant accumulation of the beta-catenin is a common event in HB, mutations or deletions in CTNNB1 (beta-catenin gene) do not always account for the high frequency of protein expression. In this study we have investigated alternative activation of beta-catenin by HGF/c-Met signaling in a large cohort of 98 HB patients enrolled in the SIOPEL-3 clinical trial. Methods: We performed immunohistochemistry, using antibodies to total beta-catenin and tyrosine654-phosphorylated beta-catenin, which is a good surrogate marker of HGF/c-Met activation. CTNNB1 mutation analysis was also carried out on all samples. We also investigated beta-catenin pathway activation in two liver cancer cell lines, HuH-6 and HuH-7. Results: Aberrant beta-catenin expression was seen in the cytoplasm and/or nucleus of 87% of tumour samples. Our results also revealed a large subset of HB, 83%, with cytoplasmic expression of tyrosine654-phosphorylated beta-catenin and 30% showing additional nuclear accumulation. Sequence analysis revealed mutations in 15% of our cohort. Statistical analysis showed an association between nuclear expression of c-Met-activated beta-catenin and wild type CTNNB1 (P-value = 0.015). Analysis of total beta-catenin and Y654-beta-catenin in response to HGF activation in the cell lines, mirrors that observed in our HB tumour cohort. Results: We identified a significant subset of hepatoblastoma patients for whom targeting of the c-Met pathway may be a treatment option and also demonstrate distinct mechanisms of beta-catenin activation in HB.
DOI Link: 10.1186/1756-9966-30-96
eISSN: 1756-9966
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2011 Purcell et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Appears in Collections:Published Articles, Dept. of Health Sciences

Files in This Item:
File Description SizeFormat 
10.1186_1756-9966-30-96.pdf774.48 kBAdobe PDFView/Open

Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.