HGF/c-Met related activation of β-catenin in hepatoblastoma
<p>Abstract</p> <p>Background</p> <p>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-c...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2011-10-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Online Access: | http://www.jeccr.com/content/30/1/96 |
| _version_ | 1818233730022506496 |
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| author | Turner Clinton Miles Carina Maibach Rudolf Childs Margaret Purcell Rachel Zimmermann Arthur Sullivan Michael |
| author_facet | Turner Clinton Miles Carina Maibach Rudolf Childs Margaret Purcell Rachel Zimmermann Arthur Sullivan Michael |
| author_sort | Turner Clinton |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Results</p> <p>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.</p> |
| first_indexed | 2024-12-12T11:26:49Z |
| format | Article |
| id | doaj.art-a70ecbc6909248ad86e2a6701fc85355 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-12T11:26:49Z |
| publishDate | 2011-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-a70ecbc6909248ad86e2a6701fc853552022-12-22T00:25:54ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662011-10-013019610.1186/1756-9966-30-96HGF/c-Met related activation of β-catenin in hepatoblastomaTurner ClintonMiles CarinaMaibach RudolfChilds MargaretPurcell RachelZimmermann ArthurSullivan Michael<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Results</p> <p>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.</p>http://www.jeccr.com/content/30/1/96 |
| spellingShingle | Turner Clinton Miles Carina Maibach Rudolf Childs Margaret Purcell Rachel Zimmermann Arthur Sullivan Michael HGF/c-Met related activation of β-catenin in hepatoblastoma Journal of Experimental & Clinical Cancer Research |
| title | HGF/c-Met related activation of β-catenin in hepatoblastoma |
| title_full | HGF/c-Met related activation of β-catenin in hepatoblastoma |
| title_fullStr | HGF/c-Met related activation of β-catenin in hepatoblastoma |
| title_full_unstemmed | HGF/c-Met related activation of β-catenin in hepatoblastoma |
| title_short | HGF/c-Met related activation of β-catenin in hepatoblastoma |
| title_sort | hgf c met related activation of β catenin in hepatoblastoma |
| url | http://www.jeccr.com/content/30/1/96 |
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