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

Nature Medicine volume 10, pages 245247 (2004) | Download Citation

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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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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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Affiliations

  1. Department of Medicine, The Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6838, USA.

    • Rajnish A Gupta
    • , Dingzhi Wang
    • , Sharada Katkuri
    •  & Raymond N DuBois
  2. Departments of Pediatrics and Cell and Developmental Biology, The Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6838, USA.

    • Haibin Wang
    • , Sudhansu K Dey
    •  & Raymond N DuBois
  3. Department of Cancer Biology, The Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6838, USA.

    • Raymond N DuBois

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The authors declare no competing financial interests.

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Correspondence to Raymond N DuBois.

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DOI

https://doi.org/10.1038/nm993

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