Kaiso-deficient mice show resistance to intestinal cancer.
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.
Prokhortchouk
Anna
A
Wellcome Trust Centre for Cell Biology, The King's Buildings, Edinburgh University, Edinburgh EH9 3JR, United Kingdom.
Sansom
Owen
O
Selfridge
Jim
J
Caballero
Isabel M
IM
Salozhin
Sergey
S
Aithozhina
Dana
D
Cerchietti
Leandro
L
Meng
Fan Guo
FG
Augenlicht
Leonard H
LH
Mariadason
John M
JM
Hendrich
Brian
B
Melnick
Ari
A
Prokhortchouk
Egor
E
Clarke
Alan
A
Bird
Adrian
A
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D018390:Gene Targeting; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009474:Neurons / Q000166:cytology; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation
D014157:Transcription Factors; C118822:Zbtb33 protein, mouse