RRC ID 27179
Author Schreiber S, Rignall B, Braeuning A, Marx-Stoelting P, Ott T, Buchmann A, Hammad S, Hengstler JG, Schwarz M, Köhle C.
Title Phenotype of single hepatocytes expressing an activated version of β-catenin in liver of transgenic mice.
Journal J Mol Histol
Abstract 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.
Volume 42(5)
Pages 393-400
Published 2011-10-1
DOI 10.1007/s10735-011-9342-6
PMID 21822615
MeSH Animals Cell Transformation, Neoplastic / pathology Gene Expression Regulation Hepatocytes / metabolism* Hepatocytes / pathology Humans Immunohistochemistry Liver / metabolism* Liver / pathology Mice Mice, Transgenic Mutant Proteins / metabolism Phenotype RNA, Messenger / genetics RNA, Messenger / metabolism beta Catenin / genetics beta Catenin / metabolism*
IF 2.531
Times Cited 17
DNA material pCALNL5 (RDB01862)