Kaiso-deficient mice show resistance to intestinal cancer

Anna Prokhortchouk, Owen Sansom, Jim Selfridge, Isabel M. Caballero, Sergey Salozhin, Dana Aithozhina, Leandro Cerchietti, Fan Guo Meng, Leonard H. Augenlicht, John M. Mariadason, Brian Hendrich, Ari Melnick, Egor Prokhortchouk, Alan Clarke, Adrian Bird

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127 Scopus citations

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 ApcMin/+ 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.

Original languageEnglish (US)
Pages (from-to)199-208
Number of pages10
JournalMolecular and cellular biology
Volume26
Issue number1
DOIs
StatePublished - Jan 1 2006

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Prokhortchouk, A., Sansom, O., Selfridge, J., Caballero, I. M., Salozhin, S., Aithozhina, D., Cerchietti, L., Meng, F. G., Augenlicht, L. H., Mariadason, J. M., Hendrich, B., Melnick, A., Prokhortchouk, E., Clarke, A., & Bird, A. (2006). Kaiso-deficient mice show resistance to intestinal cancer. Molecular and cellular biology, 26(1), 199-208. https://doi.org/10.1128/MCB.26.1.199-208.2006