| 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
|
|
WOS Category
|
CELL BIOLOGY
|
| Resource |
| DNA material |
pCALNL5 (RDB01862) |
