| Phenotype of single hepatocytes expressing an activated version of β-catenin in liver of transgenic mice. | |
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MedLine Citation:
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PMID: 21822615 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The gene CTNNB1 encoding β-catenin is mutated in about 30% of hepatocellular carcinoma, generally often combined with other genetic alterations. In transgenic mice, it has been shown that activation of β-catenin in more than 70% of all hepatocytes causes immediate proliferation leading to hepatomegaly. In this study we established a novel mouse model where β-catenin is activated only in individual, dispersed hepatocytes. Hepatocyte-specific expression of activated point-mutated β-catenin (human β-catenin(S33Y)) was established using the Cre/loxP system. Expression of several downstream targets of β-catenin signaling such as glutamine synthetase and several cytochrome P450 isoforms was confirmed by immunostaining. Only a minor portion of hepatocytes expressed the β-catenin(S33Y) transgene, which were mainly positioned as dispersed individual cells within the normal liver parenchyma. The hepatocytes with activated β-catenin did not show increased proliferation and the mice did not develop hepatomegaly. In conclusion, activated β-catenin in single hepatocytes induces a gene expression pattern in hepatocytes which is similar to that of Ctnnb1-mutated mouse liver tumors, but is apparently not sufficient to induce increased cell proliferation. Therefore, onset of proliferation seems to require concomitant activation of β-catenin in clusters of hepatocytes, suggesting a role of cell-cell communication in this process. |
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Authors:
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Sandra Schreiber; Benjamin Rignall; Albert Braeuning; Philip Marx-Stoelting; Thomas Ott; Albrecht Buchmann; Seddik Hammad; Jan G Hengstler; Michael Schwarz; Christoph Köhle |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-6 |
Journal Detail:
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Title: Journal of molecular histology Volume: - ISSN: 1567-2387 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-8-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101193653 Medline TA: J Mol Histol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, University of Tübingen, Wilhelmstr. 56, 72074, Tübingen, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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