Overexpression of the POZ-ZF protein Kaiso promotes intestinal tumorigenesis in murine models.

Over the past decade, several emerging roles for the transcription factor Kaiso in signaling and tumorigenesis have been unveiled. Intestinal-specific Kaiso overexpression induced chronic intestinal inflammation and potentiated intestinal tumorigenesis. This was consistent with the fact that Kaiso's binding partner, p120ctn, inhibits and modulates Kaiso's transcriptional activity and acts in an anti-inflammatory and anti-tumorigenic manner in murine intestinal models. However, the Kaiso-p120ctn relationship and mechanism of action in intestinal inflammation and tumorigenesis has yet to be fully explored. In this pilot study we examined whether Kaiso overexpression in conjunction with p120ctn depletion would induce severe intestinal inflammation and accelerate tumor formation. We mated intestinal Kaiso overexpressing mice (KaisoTg) with tamoxifen-inducible p120ctn conditional knockout (p120CKO) mice. Examination of intestinal tissues from the KaisoTg; p120CKO mice revealed approximately 5% and 15% depletion of p120ctn in the small and large intestine respectively at 2 months post-induction. However, as the KaisoTg; p120CKO mice aged, the p120ctn depletion only persisted in the large intestine (study endpoints at 6- and 12-months post-tamoxifen injection). Interestingly, both KaisoTg and KaisoTg;p120CKO mice presented with adenomas in the small intestine at 12 months post injection. Our findings thus suggests that Kaiso may be driving tumor formation through mechanisms independent of p120ctn loss.