PPARδ status and Apc-mediated tumourigenesis in the mouse intestine

Karen R. Reed; Owen J. Sansom; Anthony J. Hayes; Andreas J. Gescher; Douglas J. Winton; Jeffrey M. Peters; Alan R. Clarke

doi:10.1038/sj.onc.1208143

PPARδ status and Apc-mediated tumourigenesis in the mouse intestine

Karen R. Reed, Owen J. Sansom, Anthony J. Hayes, Andreas J. Gescher, Douglas J. Winton, Jeffrey M. Peters, Alan R. Clarke

Research output: Contribution to journal › Article › peer-review

106 Scopus citations

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 Apc ^MinPPARδ-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.

Original language	English (US)
Pages (from-to)	8992-8996
Number of pages	5
Journal	Oncogene
Volume	23
Issue number	55
DOIs	https://doi.org/10.1038/sj.onc.1208143
State	Published - Nov 25 2004

All Science Journal Classification (ASJC) codes

Molecular Biology
Genetics
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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@article{81a999575b664ebf9760c731f2b2606b,

title = "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 Apc MinPPARδ-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.",

author = "Reed, {Karen R.} and Sansom, {Owen J.} and Hayes, {Anthony J.} and Gescher, {Andreas J.} and Winton, {Douglas J.} and Peters, {Jeffrey M.} and Clarke, {Alan R.}",

note = "Funding Information: 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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doi = "10.1038/sj.onc.1208143",

language = "English (US)",

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T1 - PPARδ status and Apc-mediated tumourigenesis in the mouse intestine

AU - Reed, Karen R.

AU - Sansom, Owen J.

AU - Hayes, Anthony J.

AU - Gescher, Andreas J.

AU - Winton, Douglas J.

AU - Peters, Jeffrey M.

AU - Clarke, Alan R.

N1 - Funding Information: 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.

PY - 2004/11/25

Y1 - 2004/11/25

N2 - 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 Apc MinPPARδ-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.

AB - 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 Apc MinPPARδ-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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JO - Oncogene

JF - Oncogene

IS - 55

ER -

PPARδ status and Apc-mediated tumourigenesis in the mouse intestine

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

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