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PPARδ status and Apc-mediated tumourigenesis in the mouse intestine

Abstract

Based on recent reports that peroxisome proliferator-activated receptor delta (PPARδ) activation promotes tumourigenesis, we have investigated the role of this protein in Apc-mediated intestinal tumourigenesis. We demonstrate that the inactivation of Apc in the adult small intestine, while causing the expected nuclear accumulation of β-catenin, does not cause the expected increase in PPARδ mRNA or protein but conversely, the levels of PPARδ mRNA and protein are lowered. Furthermore, we find that ApcMinPPARδ-null mice exhibit an increased predisposition to intestinal tumourigenesis. Our data suggest that PPARδ is not directly regulated by β-catenin, and that inhibition of PPARδ activity is unlikely to be an appropriate strategy for the chemoprevention or chemotherapy of intestinal malignancies.

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Acknowledgements

We thank Derek Scarborough and Mark Bishop for technical assistance, and also Inke Nathke and Ian Newton for assistance with Western analysis. This work was supported by a programme grant from Cancer Research UK, a grant from the CR-UK New Targets Initiative and the Wales Gene Park.

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Correspondence to Alan R Clarke.

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Supplementary information accompanies the paper on Oncogene website (http://www.nature.com/onc).

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Reed, K., Sansom, O., Hayes, A. et al. PPARδ status and Apc-mediated tumourigenesis in the mouse intestine. Oncogene 23, 8992–8996 (2004). https://doi.org/10.1038/sj.onc.1208143

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