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Published on: September 11, 2012
Kaiso-deficient mice show resistance to intestinal cancer
Anna Prokhortchouk1, Owen Sansom, Jim Selfridge
1Wellcome Trust Centre for Cell Biology, The King's Buildings, Edinburgh University, Edinburgh EH9 3JR, United Kingdom.
Abstract:
Kaiso is a BTB domain protein that associates with the signaling molecule p120-catenin and binds to the methylated sequence mCGmCG or the nonmethylated sequence CTGCNA to modulate transcription. In Xenopus laevis, xKaiso deficiency leads to embryonic death accompanied by premature gene activation in blastulae and upregulation of the xWnt11 gene. Kaiso has also been proposed to play an essential role in mammalian synapse-specific transcription. We disrupted the Kaiso gene in mice to assess its role in mammalian development. Kaiso-null mice were viable and fertile, with no detectable abnormalities of development or gene expression. However, when crossed with tumor-susceptible Apc(Min/+) mice, Kaiso-null mice showed a delayed onset of intestinal tumorigenesis. Kaiso was found to be upregulated in murine intestinal tumors and is expressed in human colon cancers. Our data suggest that Kaiso plays a role in intestinal cancer and may therefore represent a potential target for therapeutic intervention.
Insights
Kaiso, a transcription factor, does not affect normal mouse development but delays intestinal tumor growth. Kaiso is upregulated in tumors, suggesting it is a potential therapeutic target for colon cancer.
Area of Science:
- Molecular Biology
- Developmental Biology
- Cancer Biology
Background:
- Kaiso is a BTB domain protein regulating transcription via DNA binding.
- Kaiso interacts with p120-catenin and binds methylated or nonmethylated DNA sequences.
- Previous studies in Xenopus suggested xKaiso's essential role in embryonic development.
Purpose of the Study:
- To investigate the role of Kaiso in mammalian development and intestinal tumorigenesis.
- To assess the impact of Kaiso gene disruption in mice.
- To explore Kaiso's potential as a therapeutic target in cancer.
Main Methods:
- Gene disruption of Kaiso in mice.
- Crossbreeding Kaiso-null mice with Apc(Min/+) mice.
- Analysis of intestinal tumor development and Kaiso expression in tumors.
Main Results:
- Kaiso-null mice are viable and fertile with normal development and gene expression.
- Kaiso deficiency delayed intestinal tumorigenesis in Apc(Min/+) mice.
- Kaiso is upregulated in murine intestinal tumors and human colon cancers.
Conclusions:
- Kaiso plays a role in intestinal cancer development.
- Kaiso may represent a potential therapeutic target for intestinal cancers.
