Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/28492
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
Links: http://www.jeccr.com/content/30/1/96
http://hdl.handle.net/2381/28492
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 (http://creativecommons.org/licenses/by/2.0), 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

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