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Kaiso-deficient mice show resistance to intestinal cancer.

TitleKaiso-deficient mice show resistance to intestinal cancer.
Publication TypeJournal Article
Year of Publication2006
AuthorsProkhortchouk A, Sansom OJ, Selfridge J, Caballero IM, Salozhin S, Aithozhina D, Cerchietti L, Meng FGuo, Augenlicht LH, Mariadason JM, Hendrich B, Melnick A, Prokhortchouk E, Clarke A, Bird A
JournalMol Cell Biol
Date Published2006 Jan
KeywordsAnimals, Cell Differentiation, Cell Transformation, Neoplastic, Gene Deletion, Gene Expression Regulation, Neoplastic, Gene Targeting, Intestinal Neoplasms, Mice, Mice, Mutant Strains, Neurons, Phenotype, Transcription Factors, Transcriptional Activation, Up-Regulation

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.

Alternate JournalMol. Cell. Biol.
PubMed ID16354691
PubMed Central IDPMC1317619
Grant ListG0300058 / / Medical Research Council / United Kingdom
G0301154 / / Medical Research Council / United Kingdom
GR067436MA / / Wellcome Trust / United Kingdom