PPARδ status and mismatch repair mediated neoplasia in the mouse intestine

<p>Abstract</p> <p>Background</p> <p>Therapeutic regulation of PPARδ activity using selective agonists has been proposed for various disorders. However, the consequences of altered peroxisome proliferator-activated receptor delta (PPARδ) activity in the context of intes...

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Main Authors: Peters Jeffrey M, Gescher Andreas J, Hayes Anthony J, Sansom Owen J, Reed Karen R, Clarke Alan R
Format: Article
Language:English
Published: BMC 2006-05-01
Series:BMC Cancer
Online Access:http://www.biomedcentral.com/1471-2407/6/113
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author Peters Jeffrey M
Gescher Andreas J
Hayes Anthony J
Sansom Owen J
Reed Karen R
Clarke Alan R
author_facet Peters Jeffrey M
Gescher Andreas J
Hayes Anthony J
Sansom Owen J
Reed Karen R
Clarke Alan R
author_sort Peters Jeffrey M
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Therapeutic regulation of PPARδ activity using selective agonists has been proposed for various disorders. However, the consequences of altered peroxisome proliferator-activated receptor delta (PPARδ) activity in the context of intestinal tumourigenesis remain somewhat unclear. Contradictory evidence suggesting PPARδ either attenuates or potentiates intestinal neoplasia. To further investigate the PPARδ dependency of intestinal tumourigenesis, we have analysed the consequences of PPARδ deficiency upon intestinal neoplasia occurring in mice with impaired mismatch DNA repair.</p> <p>Methods</p> <p>Mice deficient for both PPARδ and the mismatch repair gene Mlh1 were produced and the incidence and severity of intestinal neoplasia recorded.</p> <p>Results</p> <p>No significant differences between the control genotypes and the double mutant genotypes were recorded indicating that deficiency of PPARδ does not modify impaired mismatch repair induced neoplasia.</p> <p>Conclusion</p> <p>In contrast with the previously observed acceleration of intestinal neoplasia in the context of the <it>Apc</it><sup><it>Min</it>/+ </sup>mouse, PPARδ deficiency does not alter the phenotype of mismatch repair deficiency. This data supports the notion that PPARδ is not required for adenoma formation and indicate that any pro-tumourigenic effect of PPARδ inactivation may be highly context dependent.</p>
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spelling doaj.art-70cb204f008f4f1dadc911c8ab6b58912022-12-22T03:25:01ZengBMCBMC Cancer1471-24072006-05-016111310.1186/1471-2407-6-113PPARδ status and mismatch repair mediated neoplasia in the mouse intestinePeters Jeffrey MGescher Andreas JHayes Anthony JSansom Owen JReed Karen RClarke Alan R<p>Abstract</p> <p>Background</p> <p>Therapeutic regulation of PPARδ activity using selective agonists has been proposed for various disorders. However, the consequences of altered peroxisome proliferator-activated receptor delta (PPARδ) activity in the context of intestinal tumourigenesis remain somewhat unclear. Contradictory evidence suggesting PPARδ either attenuates or potentiates intestinal neoplasia. To further investigate the PPARδ dependency of intestinal tumourigenesis, we have analysed the consequences of PPARδ deficiency upon intestinal neoplasia occurring in mice with impaired mismatch DNA repair.</p> <p>Methods</p> <p>Mice deficient for both PPARδ and the mismatch repair gene Mlh1 were produced and the incidence and severity of intestinal neoplasia recorded.</p> <p>Results</p> <p>No significant differences between the control genotypes and the double mutant genotypes were recorded indicating that deficiency of PPARδ does not modify impaired mismatch repair induced neoplasia.</p> <p>Conclusion</p> <p>In contrast with the previously observed acceleration of intestinal neoplasia in the context of the <it>Apc</it><sup><it>Min</it>/+ </sup>mouse, PPARδ deficiency does not alter the phenotype of mismatch repair deficiency. This data supports the notion that PPARδ is not required for adenoma formation and indicate that any pro-tumourigenic effect of PPARδ inactivation may be highly context dependent.</p>http://www.biomedcentral.com/1471-2407/6/113
spellingShingle Peters Jeffrey M
Gescher Andreas J
Hayes Anthony J
Sansom Owen J
Reed Karen R
Clarke Alan R
PPARδ status and mismatch repair mediated neoplasia in the mouse intestine
BMC Cancer
title PPARδ status and mismatch repair mediated neoplasia in the mouse intestine
title_full PPARδ status and mismatch repair mediated neoplasia in the mouse intestine
title_fullStr PPARδ status and mismatch repair mediated neoplasia in the mouse intestine
title_full_unstemmed PPARδ status and mismatch repair mediated neoplasia in the mouse intestine
title_short PPARδ status and mismatch repair mediated neoplasia in the mouse intestine
title_sort pparδ status and mismatch repair mediated neoplasia in the mouse intestine
url http://www.biomedcentral.com/1471-2407/6/113
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