Evidence map›Paper›PMID 21281430›Full record

ArticleLiver international : official journal of the International Association for the Study of the Liver2011

Effect of mutant β-catenin on liver growth homeostasis and hepatocarcinogenesis in transgenic mice.

Timothy J Stein, Adam Jochem, Katie E Holmes, Eric P Sandgren

Open access · greenAbstract readValidation Study
In one paragraph

Article in Liver international : official journal of the International Association for the Study of the Liver, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.1field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Mutant Hras(G12V) and Kras(G12D) have overlapping, but non-identical effects on hepatocyte growth and transformation frequency in transgenic mice.Liver international : official journal of the International Association for the Study of the Liver · 2012
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Timothy J SteinDepartment of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
Adam Jochem
Katie E Holmes
Eric P Sandgren
University of Wisconsin–Madison · US

Funding

INSTITUTIONAL CTSA (UW-MADISON): CLINICAL TRIALSUL1RR025011 · NCRR · UNIVERSITY OF WISCONSIN-MADISON · PI DREZNER, MARC KENNETH · 2007 to 2011
$29.5M
TRANSGENIC MODELS OF DIOXIN CARCINOGENICITY AND AH RECEPTOR FUNCTIONP01CA022484 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI BRADFIELD, CHRISTOPHER A · 1985 to 2011
$9.2M
Short-Term Research Training of Veterinary Students in WisconsinT35OD011078 · OD · UNIVERSITY OF WISCONSIN-MADISON · PI BJORLING, DALE EDMOND, JORGENSEN, JOAN S · 2012 to 2025
$1.0M
Effects of mutant beta-catenin on hepatocellular cancerK01RR020033 · NCRR · UNIVERSITY OF WISCONSIN-MADISON · PI STEIN, TIMOTHY J · 2005 to 2006
$187k
NCI NIH HHS P01 CA022484NCI NIH HHS P01-CA022484NCI NIH HHS R01-CA07671NCRR NIH HHS 1UL1RR025011NCRR NIH HHS K01 RR020033NCRR NIH HHS K01-RR020033NCRR NIH HHS UL1 RR025011NIH HHS T35 OD011078
6 · The paper itself

Abstract

backgroundMutations in the Wnt signalling pathway molecule β-catenin are associated with liver cancer.

aimsOur aim was to confirm the effects of stabilized β-catenin on liver growth, identify whether those effects were reversible and cell autonomous or non-cell autonomous and to model β-catenin-induced liver cancer in mice.

methodsUsing a liver-specific inducible promoter, we generated transgenic mice in which the expression of mutant β-catenin can be induced or repressed within hepatocytes in mice of different ages.

resultsSimilar to other models, the hepatic expression of mutant β-catenin in our model beginning in utero or induced in quiescent adult liver resulted in a two-fold liver enlargement and development of disease with a latency of 1-5 months, and mice displayed elevated blood ammonia and altered hepatic gene expression. Our model additionally allowed us to discover that molecular and phenotypic abnormalities were reversible following the inhibition of transgene expression. Hepatocyte transplant studies indicated that mutant β-catenin could not increase the growth of transgene-expressing foci in either growth-permissive or -restrictive hepatic environments, but still directly altered hepatocyte gene expression. Mice with continuous but focal transgene expression developed hepatic neoplasms after the age of 1 year.

conclusionsOur findings indicate that hepatocyte gene expression is directly affected by mutant β-catenin in a cell autonomous manner. However, hepatomegaly associated with diffuse hepatocyte-specific expression of mutant β-catenin is secondary to liver functional alteration or non-cell autonomous. Both phenotypes are reversible. Nevertheless, some foci of transgene-expressing cells progressed to carcinoma, confirming the association of mutant β-catenin with liver cancer.

Indexed as

Animalsbeta CateninCell TransplantationDoxycyclineFemaleGene Expression Regulation, NeoplasticGene Knockdown TechniquesGene SilencingHepatocytesHepatomegalyHomeostasisLiverLiver Neoplasms, ExperimentalMaleMiceMice, Transgenicbeta CateninCTNNB1 protein, mouseDoxycyclineMutant Proteins

Identifiers

PMID21281430
PMCPMC3093768
OpenAlexW1931041874

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.