The transforming growth factor-α and cyclin D1 genes are direct targets of β-catenin signaling in hepatocyte proliferation
Abstract
Background & aims β-Catenin is an oncogene frequently mutated in hepatocellular carcinoma. In this study, we investigated target genes of β-catenin signaling in hepatocyte proliferation. Methods We studied transgenic mice displaying either inactivation or activation of the β-catenin pathway, focusing on analysis of liver proliferation due to aberrant β-catenin activation, and on the regeneration process during which β-catenin signaling is transiently activated. We localized in situ the various partners involved in proliferation or identified as targets of β-catenin in these transgenic and regenerating livers. We also performed comparative transcriptome analyses, using microarrays. Finally, we extracted, from deep-sequencing data, both the DNA regulatory elements bound to the β-catenin/Tcf nuclear complex and the expression levels of critical targets identified in microarrays. Results β-Catenin activation during liver regeneration occurred during G1/S cell cycle progression and allowed zonal extension of the normal territory of active β-catenin and panlobular proliferation. We found that β-catenin controlled both cell-autonomous and non-cell-autonomous hepatocyte proliferation, through direct transcriptional and complex control of cyclin D1 gene expression and of the expression of a new target gene, Tgfα. Conclusions We propose that β-catenin controls panlobular hepatocyte proliferation partly by controlling, together with its Tcf4 nuclear partner, expression of the pro-prolif…
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Wnt/β-catenin signaling controls the G1/S transition.
“The Wnt/β-catenin signaling pathway is one of the mechanisms known to control G1/S transition (35–38).”
From Wnt signaling regulates hepatocyte cell division by a transcriptional repressor cascade (2022) · cites this paper as [38]
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Background
- Authors
- Torre, C., Benhamouche, S., Mitchell, C., Godard, C., Veber, P., Letourneur, F., Cagnard, N., Jacques, S., Finzi, L., Perret, C., & Colnot, S.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Colnot, Sabine
- ORCID
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 55
- Issue
- 1
- Pages
- 86-95
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W1986528418
- Semantic Scholar
- 6ba2b57754a4b4d0a18c9f84329ab8bdfbe5fab9
- Cited by
- 60
- References
- 0
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 7 · 2015: 3 · 2014: 3 · 2013: 4 · 2012: 9
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Keywords
- β-catenin signaling, hepatocyte proliferation, cyclin D1, transforming growth factor-alpha, TCF4, liver regeneration, hepatocellular carcinoma, transcriptional regulation, oncogenic signaling, liver transcriptome
- MeSH terms
- Animals, Base Sequence, Cell Cycle, DNA, Liver, Liver Regeneration, Mice, Inbred C57BL, Mice, Transgenic, Models, Biological, Molecular Sequence Data, Signal Transduction, Transforming Growth Factor alpha, Mice, Knockout, Genes, bcl-1, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Hepatocytes, Cell Proliferation, beta Catenin, Mice
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