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Activation of nuclear hormone receptor peroxisome proliferator–activated receptor-δ accelerates intestinal adenoma growth

Abstract

We treated Apcmin mice, which are predisposed to intestinal polyposis, with a selective synthetic agonist of peroxisome proliferator–activated receptor-δ (PPAR-δ). Exposure of Apcmin mice to the PPAR-δ ligand GW501516 resulted in a significant increase in the number and size of intestinal polyps. The most prominent effect was on polyp size; mice treated with the PPAR-δ activator had a fivefold increase in the number of polyps larger than 2 mm. Our results implicate PPAR-δ in the regulation of intestinal adenoma growth.

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Figure 1: Effect of a PPAR-δ agonist on intestinal polyposis.

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Acknowledgements

Mice were housed in accordance with institutional and NIH guidelines. This work is supported in part by US Public Health Services grants RO1DK 47279 and P0-CA-77839 to R.N.D. and HD 33994 to S.K.D. R.N.D. is a Hortense B. Ingram Professor of Molecular Oncology. R.N.D. (R37-DK47297) and S.K.D. (R37-HD12304) are recipients of National Institutes of Health MERIT awards. We thank the T.J. Martell Foundation and the National Colorectal Cancer Research Alliance for their generous support to R.N.D. Histological analysis was performed by K. Washington (pathologist).

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Correspondence to Raymond N DuBois.

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Gupta, R., Wang, D., Katkuri, S. et al. Activation of nuclear hormone receptor peroxisome proliferator–activated receptor-δ accelerates intestinal adenoma growth. Nat Med 10, 245–247 (2004). https://doi.org/10.1038/nm993

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