Home LiteratureArticle Details
PMID: 18616431 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Role of peroxisome-proliferator-activated receptor beta/delta (PPARbeta/delta) in gastrointestinal tract function and disease.

Clinical science (London, England : 1979) ·Vol. 115 ·No. 4 ·2008-08-00 ·Pages 107-27

Peters JM, Hollingshead HE, Gonzalez FJ

Abstract

PPARbeta/delta (peroxisome-proliferator-activated receptor beta/delta) is one of three PPARs in the nuclear hormone receptor superfamily that are collectively involved in the control of lipid homoeostasis among other functions. PPARbeta/delta not only acts as a ligand-activated transcription factor, but also affects signal transduction by interacting with other transcription factors such as NF-kappaB (nuclear factor kappaB). Constitutive expression of PPARbeta/delta in the gastrointestinal tract is very high compared with other tissues and its potential physiological roles in this tissue include homoeostatic regulation of intestinal cell proliferation/differentiation and modulation of inflammation associated with inflammatory bowel disease and colon cancer. Analysis of mouse epithelial cells in the intestine and colon has clearly demonstrated that ligand activation of PPARbeta/delta induces terminal differentiation. The PPARbeta/delta target genes mediating this effect are currently unknown. Emerging evidence suggests that PPARbeta/delta can suppress inflammatory bowel disease through PPARbeta/delta-dependent and ligand-independent down-regulation of inflammatory signalling. However, the role of PPARbeta/delta in colon carcinogenesis remains controversial, as conflicting evidence suggests that ligand activation of PPARbeta/delta can either potentiate or attenuate this disease. In the present review, we summarize the role of PPARbeta/delta in gastrointestinal physiology and disease with an emphasis on findings in experimental models using both high-affinity ligands and null-mouse models.

MeSH Terms
Animals Cell Transformation, Neoplastic/metabolism Colonic Neoplasms/physiopathology Disease Models, Animal Gastrointestinal Tract/physiology Humans Inflammatory Bowel Diseases/physiopathology Ligands Mice Neoplasm Proteins/physiology PPAR delta/physiology PPAR-beta/physiology Rats
Chemicals
Ligands Neoplasm Proteins PPAR delta PPAR-beta
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Peters Jeffrey M
Department of Veterinary and Biomedical Sciences and The Center of Molecular Toxicology and Carcinogenesis, Pennsylvania State University, University Park, PA 16802, USA. [email protected]
Hollingshead Holly E
Gonzalez Frank J
References (179)
179 references, click to expand
  1. Anti-thrombotics in thrombosis and cancer.
    Future Oncol. 2005 Jun;1(3):395-403 PMID: 16556013
  2. Dietary fat and risk of colon and rectal cancer with aberrant MLH1 expression, APC or KRAS genes.
    Cancer Causes Control. 2007 Oct;18(8):865-79 PMID: 17636402
  3. Liver-type fatty acid-binding protein is highly expressed in intestinal metaplasia and in a subset of carcinomas of the stomach without association with the fatty acid synthase status in the carcinoma.
    Pathobiology. 2004;71(3):115-22 PMID: 15051923
  4. Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta(delta).
    Mol Cell Biol. 2000 Jul;20(14):5119-28 PMID: 10866668
  5. Alteration of gene expression in normal-appearing colon mucosa of APC(min) mice and human cancer patients.
    Cancer Res. 2004 May 15;64(10):3694-700 PMID: 15150130
  6. Molecular mechanisms of the effects of olive oil and other dietary lipids on cancer.
    Mol Nutr Food Res. 2007 Oct;51(10):1279-92 PMID: 17879998
  7. PPARbeta-mediated growth suppression of baicalein and dexamethasone in human myeloma cells.
    Leukemia. 2007 Jan;21(1):187-90 PMID: 17082776
  8. Transcriptional gene expression profiles of colorectal adenoma, adenocarcinoma, and normal tissue examined by oligonucleotide arrays.
    Cancer Res. 2001 Apr 1;61(7):3124-30 PMID: 11306497
  9. Activation of peroxisome proliferator-activated receptor (PPAR)delta promotes reversal of multiple metabolic abnormalities, reduces oxidative stress, and increases fatty acid oxidation in moderately obese men.
    Diabetes. 2008 Feb;57(2):332-9 PMID: 18024853
  10. Transforming growth factor-beta1 is a molecular target for the peroxisome proliferator-activated receptor delta.
    Circ Res. 2008 Feb 1;102(2):193-200 PMID: 18007025
  11. Rat PPARs: quantitative analysis in adult rat tissues and regulation in fasting and refeeding.
    Endocrinology. 2001 Oct;142(10):4195-202 PMID: 11564675
  12. Metabolomics reveals that hepatic stearoyl-CoA desaturase 1 downregulation exacerbates inflammation and acute colitis.
    Cell Metab. 2008 Feb;7(2):135-47 PMID: 18249173
  13. Critical roles of PPAR beta/delta in keratinocyte response to inflammation.
    Genes Dev. 2001 Dec 15;15(24):3263-77 PMID: 11751632
  14. Understanding and exploiting the endogenous interleukin-10/STAT3-mediated anti-inflammatory response.
    Curr Opin Pharmacol. 2006 Aug;6(4):379-86 PMID: 16713356
  15. Genetic disruption of PPARdelta decreases the tumorigenicity of human colon cancer cells.
    Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2598-603 PMID: 11226285
  16. PPARdelta is a very low-density lipoprotein sensor in macrophages.
    Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1268-73 PMID: 12540828
  17. Expression of the peroxisome proliferator-activated receptor (PPAR) in the mouse colonic mucosa.
    Biochem Biophys Res Commun. 1996 May 24;222(3):844-51 PMID: 8651933
  18. PPARbeta/delta potentiates PPARgamma-stimulated adipocyte differentiation.
    FASEB J. 2004 Sep;18(12):1477-9 PMID: 15247146
  19. Linoleic acid intake and cancer risk: a review and meta-analysis.
    Am J Clin Nutr. 1998 Jul;68(1):142-53 PMID: 9665108
  20. Peroxisome proliferator-activated receptor gamma ligands suppress colon carcinogenesis induced by azoxymethane in mice.
    Gastroenterology. 2003 Feb;124(2):361-7 PMID: 12557142
  21. Cellular differentiation in the emerging fetal rat small intestinal epithelium: mosaic patterns of gene expression.
    Proc Natl Acad Sci U S A. 1989 Feb;86(4):1278-82 PMID: 2645578
  22. Wnt/beta-catenin is essential for intestinal homeostasis and maintenance of intestinal stem cells.
    Mol Cell Biol. 2007 Nov;27(21):7551-9 PMID: 17785439
  23. Activation of peroxisome proliferator-activated receptor delta stimulates the proliferation of human breast and prostate cancer cell lines.
    Cancer Res. 2004 May 1;64(9):3162-70 PMID: 15126355
  24. Crosstalk between peroxisome proliferator-activated receptor delta and VEGF stimulates cancer progression.
    Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):19069-74 PMID: 17148604
  25. Oxidative metabolism of linoleic acid modulates PPAR-beta/delta suppression of PPAR-gamma activity.
    Oncogene. 2006 Feb 23;25(8):1225-41 PMID: 16288226
  26. PPARdelta modulates lipopolysaccharide-induced TNFalpha inflammation signaling in cultured cardiomyocytes.
    J Mol Cell Cardiol. 2006 Jun;40(6):821-8 PMID: 16698033
  27. PPARgamma inhibitors reduce tubulin protein levels by a PPARgamma, PPARdelta and proteasome-independent mechanism, resulting in cell cycle arrest, apoptosis and reduced metastasis of colorectal carcinoma cells.
    Int J Cancer. 2007 Feb 1;120(3):702-13 PMID: 17096328
  28. Ligand activation of peroxisome proliferator-activated receptor beta inhibits colon carcinogenesis.
    Cancer Res. 2006 Apr 15;66(8):4394-401 PMID: 16618765
  29. Gene expression profiling of potential peroxisome proliferator-activated receptor (PPAR) target genes in human hepatoblastoma cell lines inducibly expressing different PPAR isoforms.
    Nucl Recept. 2005 Oct 03;3:3 PMID: 16197558
  30. Anti-tumor effect of recombinant retroviral vector-mediated human ANGPTL4 gene transfection.
    Chin Med J (Engl). 2004 Sep;117(9):1364-9 PMID: 15377430
  31. Dietary omega-3 fats reduce proliferation and tumor yields at colorectal anastomosis in rats.
    Gastroenterology. 1995 Aug;109(2):431-9 PMID: 7615192
  32. Vitamin D and colon carcinogenesis.
    J Nutr. 2004 Dec;134(12 Suppl):3463S-3471S PMID: 15570055
  33. Dose-dependent suppression of hyperlipidemia and intestinal polyp formation in Min mice by pioglitazone, a PPAR gamma ligand.
    Cancer Sci. 2003 Nov;94(11):960-4 PMID: 14611672
  34. Effect of diets high in omega-3 and omega-6 fatty acids on initiation and postinitiation stages of colon carcinogenesis.
    Cancer Res. 1991 Jan 15;51(2):487-91 PMID: 1821094
  35. Functional relationship between MyoD and peroxisome proliferator-activated receptor-dependent regulatory pathways in the control of the human uncoupling protein-3 gene transcription.
    Mol Endocrinol. 2003 Oct;17(10):1944-58 PMID: 12843208
  36. The peroxisome proliferator activated receptor δ is required for the differentiation of THP-1 monocytic cells by phorbol ester.
    Nucl Recept. 2003 Dec 11;1:9 PMID: 14670086
  37. The PPARdelta agonist GW0742X reduces atherosclerosis in LDLR(-/-) mice.
    Atherosclerosis. 2005 Jul;181(1):29-37 PMID: 15939051
  38. Indomethacin induces apoptosis in 786-O renal cell carcinoma cells by activating mitogen-activated protein kinases and AKT.
    Eur J Pharmacol. 2007 Jun 1;563(1-3):49-60 PMID: 17341418
  39. Concomitant suppression of hyperlipidemia and intestinal polyp formation in Apc-deficient mice by peroxisome proliferator-activated receptor ligands.
    Cancer Res. 2003 Sep 15;63(18):6090-5 PMID: 14522940
  40. Peroxisome proliferator-activated receptor-beta/delta inhibits epidermal cell proliferation by down-regulation of kinase activity.
    J Biol Chem. 2005 Mar 11;280(10):9519-27 PMID: 15632134
  41. Peroxisome proliferator-activated receptor (PPAR)-beta/delta stimulates differentiation and lipid accumulation in keratinocytes.
    J Invest Dermatol. 2004 Apr;122(4):971-83 PMID: 15102088
  42. Meta-analysis of primary target genes of peroxisome proliferator-activated receptors.
    Genome Biol. 2007;8(7):R147 PMID: 17650321
  43. The effect of body weight on altered expression of nuclear receptors and cyclooxygenase-2 in human colorectal cancers.
    Nutr J. 2007 Sep 03;6:20 PMID: 17767717
  44. Tetradecylselenoacetic acid, a PPAR ligand with antioxidant, antiinflammatory, and hypolipidemic properties.
    Arterioscler Thromb Vasc Biol. 2007 Mar;27(3):628-34 PMID: 17185614
  45. U94 alters FN1 and ANGPTL4 gene expression and inhibits tumorigenesis of prostate cancer cell line PC3.
    Cancer Cell Int. 2005 Jun 22;5:19 PMID: 15972109
  46. Reduced Paneth cell alpha-defensins in ileal Crohn's disease.
    Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18129-34 PMID: 16330776
  47. Correlation between expression of peroxisome proliferator-activated receptor beta and squamous differentiation in epidermal and tracheobronchial epithelial cells.
    Mol Cell Endocrinol. 1999 Jan 25;147(1-2):85-92 PMID: 10195695
  48. Anti-metastatic prostacyclins inhibit the adhesion of colon carcinoma to endothelial cells by blocking E-selectin expression.
    Clin Exp Metastasis. 1996 May;14(3):230-8 PMID: 8674277
  49. Genomic organization of the mouse peroxisome proliferator-activated receptor beta/delta gene: alternative promoter usage and splicing yield transcripts exhibiting differential translational efficiency.
    Biochem J. 2002 Sep 15;366(Pt 3):767-75 PMID: 12059785
  50. Liver fatty acid binding protein expression in colorectal neoplasia.
    Br J Cancer. 2004 May 17;90(10):1955-60 PMID: 15138477
  51. Antiapoptotic role of PPARbeta in keratinocytes via transcriptional control of the Akt1 signaling pathway.
    Mol Cell. 2002 Oct;10(4):721-33 PMID: 12419217
  52. COX-2 suppresses tissue factor expression via endocannabinoid-directed PPARdelta activation.
    J Exp Med. 2007 Sep 3;204(9):2053-61 PMID: 17724132
  53. Identification of silencing of nine genes in human gastric cancers.
    Cancer Res. 2002 Nov 15;62(22):6645-50 PMID: 12438262
  54. Prostaglandin E(2) promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor delta.
    Cancer Cell. 2004 Sep;6(3):285-95 PMID: 15380519
  55. Peroxisome proliferator-activated receptor beta/delta activation improves angiotensin II-induced cardiac hypertrophy in vitro.
    Clin Exp Hypertens. 2008 Feb;30(2):109-19 PMID: 18293166
  56. Inhibition of interleukin-1beta-induced group IIA secretory phospholipase A2 expression by peroxisome proliferator-activated receptors (PPARs) in rat vascular smooth muscle cells: cooperation between PPARbeta and the proto-oncogene BCL-6.
    Mol Cell Biol. 2007 Dec;27(23):8374-87 PMID: 17908795
  57. Bezafibrate is a dual ligand for PPARalpha and PPARbeta: studies using null mice.
    Biochim Biophys Acta. 2003 Jun 10;1632(1-3):80-9 PMID: 12782154
  58. The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells.
    Cell. 2002 Oct 18;111(2):241-50 PMID: 12408868
  59. Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) ligands inhibit growth of UACC903 and MCF7 human cancer cell lines.
    Toxicology. 2008 Jan 14;243(1-2):236-43 PMID: 18054822
  60. PPARbeta/delta protects against experimental colitis through a ligand-independent mechanism.
    Dig Dis Sci. 2007 Nov;52(11):2912-9 PMID: 17404849
  61. ERK5 activation inhibits inflammatory responses via peroxisome proliferator-activated receptor delta (PPARdelta) stimulation.
    J Biol Chem. 2006 Oct 27;281(43):32164-74 PMID: 16943204
  62. Expression of peroxisome proliferator-activated receptor delta in human gastric cancer and its response to specific COX-2 inhibitor.
    Cancer Lett. 2005 Jun 1;223(1):11-7 PMID: 15890232
  63. The expression of PPAR-associated genes is modulated through postnatal development of PPAR subtypes in the small intestine.
    Biochim Biophys Acta. 2001 Mar 30;1531(1-2):68-76 PMID: 11278173
  64. The 15-lipoxygenase-1 product 13-S-hydroxyoctadecadienoic acid down-regulates PPAR-delta to induce apoptosis in colorectal cancer cells.
    Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9968-73 PMID: 12909723
  65. Peroxisome proliferator-activated receptor activators inhibit thrombin-induced endothelin-1 production in human vascular endothelial cells by inhibiting the activator protein-1 signaling pathway.
    Circ Res. 1999 Sep 3;85(5):394-402 PMID: 10473669
  66. Differential expression of peroxisome proliferator-activated receptors (PPARs) in the developing human fetal digestive tract.
    J Histochem Cytochem. 2000 May;48(5):603-11 PMID: 10769044
  67. Role of prostacyclin versus peroxisome proliferator-activated receptor beta receptors in prostacyclin sensing by lung fibroblasts.
    Am J Respir Cell Mol Biol. 2006 Feb;34(2):242-6 PMID: 16239641
  68. Quantitative analysis of PPARdelta mRNA by real-time RT-PCR in 86 rectal cancer tissues.
    Eur J Surg Oncol. 2006 Mar;32(2):181-5 PMID: 16361076
  69. PPARbeta agonists trigger neuronal differentiation in the human neuroblastoma cell line SH-SY5Y.
    J Cell Physiol. 2007 Jun;211(3):837-47 PMID: 17390299
  70. PPARalpha and PPARdelta activators inhibit cytokine-induced nuclear translocation of NF-kappaB and expression of VCAM-1 in EAhy926 endothelial cells.
    Eur J Pharmacol. 2002 Jan 25;435(2-3):143-51 PMID: 11821020
  71. PPARbeta/delta selectively induces differentiation and inhibits cell proliferation.
    Cell Death Differ. 2006 Jan;13(1):53-60 PMID: 16021179
  72. Reevaluation of the PPAR-beta/delta ligand binding domain model reveals why it exhibits the activated form.
    Mol Cell. 2006 Jan 6;21(1):1-2 PMID: 16387648
  73. Selective binding site for [3H]prostacyclin on platelets.
    J Clin Invest. 1979 Feb;63(2):215-20 PMID: 372237
  74. Peroxisome proliferator-activated receptor beta (delta)-dependent regulation of ubiquitin C expression contributes to attenuation of skin carcinogenesis.
    J Biol Chem. 2004 May 28;279(22):23719-27 PMID: 15033975
  75. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat.
    Endocrinology. 1996 Jan;137(1):354-66 PMID: 8536636
  76. Activation of PPARbeta/delta induces endothelial cell proliferation and angiogenesis.
    Arterioscler Thromb Vasc Biol. 2007 Jan;27(1):63-9 PMID: 17068288
  77. Induction of PPARbeta and prostacyclin (PGI2) synthesis by Raf signaling: failure of PGI2 to activate PPARbeta.
    FEBS J. 2006 Jan;273(1):170-9 PMID: 16367757
  78. The oxidative stress mediator 4-hydroxynonenal is an intracellular agonist of the nuclear receptor peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta).
    Free Radic Biol Med. 2007 Apr 15;42(8):1155-64 PMID: 17382197
  79. Prostacyclin-mediated activation of peroxisome proliferator-activated receptor delta in colorectal cancer.
    Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13275-80 PMID: 11087869
  80. Effect of dietary eicosapentaenoic acid on azoxymethane-induced colon carcinogenesis in rats.
    Cancer Res. 1988 Sep 1;48(17):4790-4 PMID: 2842039
  81. Increased levels of PPARbeta/delta and cyclin D1 in flat dysplastic ACF and adenomas in Apc(Min/+) mice.
    Anticancer Res. 2005 Nov-Dec;25(6B):3781-9 PMID: 16309164
  82. A critical role for the peroxisome proliferator-activated receptor alpha (PPARalpha) in the cellular fasting response: the PPARalpha-null mouse as a model of fatty acid oxidation disorders.
    Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7473-8 PMID: 10377439
  83. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors.
    Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7355-9 PMID: 8041794
  84. Activators of the nuclear receptor PPARgamma enhance colon polyp formation.
    Nat Med. 1998 Sep;4(9):1058-61 PMID: 9734400
  85. The human peroxisome proliferator-activated receptor delta gene is a primary target of 1alpha,25-dihydroxyvitamin D3 and its nuclear receptor.
    J Mol Biol. 2005 Jun 3;349(2):248-60 PMID: 15890193
  86. Isoform specific changes in PPAR alpha and beta in colon and breast cancer with differentiation.
    Biochem Biophys Res Commun. 2006 Feb 10;340(2):656-60 PMID: 16378595
  87. The role of IL-6 and STAT3 in inflammation and cancer.
    Eur J Cancer. 2005 Nov;41(16):2502-12 PMID: 16199153
  88. Effects of intestinal fatty acid-binding protein overexpression on fatty acid metabolism in Caco-2 cells.
    J Lipid Res. 2000 Jan;41(1):84-92 PMID: 10627505
  89. Manipulation of pulmonary prostacyclin synthase expression prevents murine lung cancer.
    Cancer Res. 2002 Feb 1;62(3):734-40 PMID: 11830527
  90. Tissue factor and fibrin in tumor angiogenesis.
    Semin Thromb Hemost. 2004 Feb;30(1):31-44 PMID: 15034796
  91. Effects of di(2-ethylhexyl) phthalate, a widely used peroxisome proliferator and plasticizer, on cell growth in the human keratinocyte cell line NCTC 2544.
    J Toxicol Environ Health A. 2006 Mar;69(5):353-65 PMID: 16455614
  92. Peroxisome proliferator-activated receptor beta/delta activation inhibits hypertrophy in neonatal rat cardiomyocytes.
    Cardiovasc Res. 2005 Mar 1;65(4):832-41 PMID: 15721863
  93. Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting.
    J Clin Invest. 1999 Jun;103(11):1489-98 PMID: 10359558
  94. The toxicology of ligands for peroxisome proliferator-activated receptors (PPAR).
    Toxicol Sci. 2006 Apr;90(2):269-95 PMID: 16322072
  95. Pulmonary prostacyclin synthase overexpression chemoprevents tobacco smoke lung carcinogenesis in mice.
    Cancer Res. 2004 Aug 15;64(16):5897-904 PMID: 15313935
  96. Increased infarct size and lack of hyperphagic response after focal cerebral ischemia in peroxisome proliferator-activated receptor beta-deficient mice.
    J Cereb Blood Flow Metab. 2006 Mar;26(3):433-45 PMID: 16094319
  97. Effects of bezafibrate, PPAR pan-agonist, and GW501516, PPARdelta agonist, on development of steatohepatitis in mice fed a methionine- and choline-deficient diet.
    Eur J Pharmacol. 2006 Apr 24;536(1-2):182-91 PMID: 16574099
  98. Deficiency of PPARbeta/delta in the epidermis results in defective cutaneous permeability barrier homeostasis and increased inflammation.
    J Invest Dermatol. 2008 Feb;128(2):370-7 PMID: 17713572
  99. NO-donating aspirin isomers downregulate peroxisome proliferator-activated receptor (PPAR)delta expression in APC(min/+) mice proportionally to their tumor inhibitory effect: Implications for the role of PPARdelta in carcinogenesis.
    Carcinogenesis. 2006 Feb;27(2):232-9 PMID: 16141240
  100. Peroxisome proliferator-activated receptor expression and activation in normal human colonic epithelial cells and tubular adenomas.
    Scand J Gastroenterol. 2005 Feb;40(2):198-205 PMID: 15764152
  101. Anti-inflammatory actions of PPAR ligands: new insights on cellular and molecular mechanisms.
    Trends Immunol. 2007 Dec;28(12):551-8 PMID: 17981503
  102. Nonsteroidal anti-inflammatory drugs induce colorectal cancer cell apoptosis by suppressing 14-3-3epsilon.
    Cancer Res. 2007 Apr 1;67(7):3185-91 PMID: 17409426
  103. Alteration of gene expression in macroscopically normal colonic mucosa from individuals with a family history of sporadic colon cancer.
    Clin Cancer Res. 2005 Feb 15;11(4):1400-7 PMID: 15746039
  104. PPAR delta agonists stimulate oligodendrocyte differentiation in tissue culture.
    Glia. 2001 Mar 1;33(3):191-204 PMID: 11241737
  105. Molecular diversity of prostanoid receptors; subtypes and isoforms of prostaglandin E receptor.
    Adv Exp Med Biol. 1997;400A:207-13 PMID: 9547559
  106. Identification of the modifier of Min 2 (Mom2) locus, a new mutation that influences Apc-induced intestinal neoplasia.
    Genome Res. 2002 Jan;12(1):88-97 PMID: 11779834
  107. PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs.
    Cell. 1999 Oct 29;99(3):335-45 PMID: 10555149
  108. Indomethacin induces differential expression of beta-catenin, gamma-catenin and T-cell factor target genes in human colorectal cancer cells.
    Carcinogenesis. 2002 Jan;23(1):107-14 PMID: 11756231
  109. Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta.
    Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4312-7 PMID: 9113986
  110. Conjugated linoleic acid activates peroxisome proliferator-activated receptor alpha and beta subtypes but does not induce hepatic peroxisome proliferation in Sprague-Dawley rats.
    Biochim Biophys Acta. 1999 Jan 4;1436(3):331-42 PMID: 9989264
  111. Sulindac sulfone is most effective in modulating beta-catenin-mediated transcription in cells with mutant APC.
    Ann N Y Acad Sci. 2005 Nov;1059:41-55 PMID: 16382042
  112. Peroxisome proliferator-activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappaB and AP-1.
    J Biol Chem. 1999 Nov 5;274(45):32048-54 PMID: 10542237
  113. Peroxisome proliferator-activated receptor delta as a molecular target to regulate lung cancer cell growth.
    FEBS Lett. 2005 Jul 4;579(17):3829-36 PMID: 15978581
  114. Protective effect of nonsteroidal anti-inflammatory drugs on colorectal adenomas is modified by a polymorphism in peroxisome proliferator-activated receptor delta.
    Pharmacogenet Genomics. 2006 Jan;16(1):43-50 PMID: 16344721
  115. Activation of the peroxisome proliferator-activated receptor gamma promotes the development of colon tumors in C57BL/6J-APCMin/+ mice.
    Nat Med. 1998 Sep;4(9):1053-7 PMID: 9734399
  116. Peroxisome proliferator-activated receptor alpha, delta, gamma1 and gamma2 expressions are present in human monocyte-derived dendritic cells and modulate dendritic cell maturation by addition of subtype-specific ligands.
    Scand J Immunol. 2006 May;63(5):330-7 PMID: 16640656
  117. The effects of fish oil, olive oil, oleic acid and linoleic acid on colorectal neoplastic processes.
    Clin Nutr. 2003 Feb;22(1):71-9 PMID: 12553953
  118. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators.
    Nature. 1990 Oct 18;347(6294):645-50 PMID: 2129546
  119. Thromboxanes and prostacyclin: positive and negative modulators of tumor growth.
    Biochem Biophys Res Commun. 1981 Oct 30;102(4):1122-9 PMID: 6274330
  120. Peroxisome-proliferator-activated receptors and cancers: complex stories.
    Nat Rev Cancer. 2004 Jan;4(1):61-70 PMID: 14708026
  121. Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration.
    Genes Dev. 2004 Jun 15;18(12):1385-90 PMID: 15198980
  122. Prostacyclin induces apoptosis of vascular smooth muscle cells by a cAMP-mediated inhibition of extracellular signal-regulated kinase activity and can counteract the mitogenic activity of endothelin-1 or basic fibroblast growth factor.
    Circ Res. 2004 Apr 2;94(6):759-67 PMID: 14963006
  123. Angiopoietin-like 4 is a proangiogenic factor produced during ischemia and in conventional renal cell carcinoma.
    Am J Pathol. 2003 May;162(5):1521-8 PMID: 12707035
  124. Activation of PPARdelta inhibits cardiac fibroblast proliferation and the transdifferentiation into myofibroblasts.
    Cardiovasc Res. 2007 Aug 1;75(3):519-29 PMID: 17543901
  125. PPARdelta status and Apc-mediated tumourigenesis in the mouse intestine.
    Oncogene. 2004 Nov 25;23(55):8992-6 PMID: 15480419
  126. Modulation of the expression of peroxisome proliferators-activated receptors in human fibroblasts.
    Fertil Steril. 2007 Mar;87(3):706-9 PMID: 17156782
  127. Ligand activation of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) and inhibition of cyclooxygenase 2 (COX2) attenuate colon carcinogenesis through independent signaling mechanisms.
    Carcinogenesis. 2008 Jan;29(1):169-76 PMID: 17893232
  128. Expression of PPARdelta in multistage carcinogenesis of the colorectum: implications of malignant cancer morphology.
    Br J Cancer. 2006 Oct 9;95(7):889-95 PMID: 16969348
  129. Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects.
    J Biol Chem. 1999 Mar 5;274(10):6718-25 PMID: 10037770
  130. Expression profiling of peroxisome proliferator-activated receptor-delta (PPAR-delta) in mouse tissues using tissue microarray.
    Histochem Cell Biol. 2007 May;127(5):485-94 PMID: 17333240
  131. Crypt-restricted proliferation and commitment to the Paneth cell lineage following Apc loss in the mouse intestine.
    Development. 2005 Mar;132(6):1443-51 PMID: 15716339
  132. The nuclear eicosanoid receptor, PPARgamma, is aberrantly expressed in colonic cancers.
    Carcinogenesis. 1998 Jan;19(1):49-53 PMID: 9472692
  133. Differential involvement of peroxisome-proliferator-activated receptors alpha and delta in fibrate and fatty-acid-mediated inductions of the gene encoding liver fatty-acid-binding protein in the liver and the small intestine.
    Biochem J. 2001 Apr 15;355(Pt 2):481-8 PMID: 11284737
  134. Inhibition of angiogenesis and vascular leakiness by angiopoietin-related protein 4.
    Cancer Res. 2003 Oct 15;63(20):6651-7 PMID: 14583458
  135. The direct peroxisome proliferator-activated receptor target fasting-induced adipose factor (FIAF/PGAR/ANGPTL4) is present in blood plasma as a truncated protein that is increased by fenofibrate treatment.
    J Biol Chem. 2004 Aug 13;279(33):34411-20 PMID: 15190076
  136. Induction of differentiation in F9 cells and activation of peroxisome proliferator-activated receptor delta by valproic acid and its teratogenic derivatives.
    Mol Pharmacol. 2001 May;59(5):1269-76 PMID: 11306712
  137. Prostacyclin and its analogues: antimetastatic effects and mechanisms of action.
    Cancer Metastasis Rev. 1994 Dec;13(3-4):349-64 PMID: 7712596
  138. Suppression of pro-inflammatory adhesion molecules by PPAR-delta in human vascular endothelial cells.
    Arterioscler Thromb Vasc Biol. 2008 Feb;28(2):315-21 PMID: 18048767
  139. Mechanisms of cancer-induced thrombosis in cancer.
    Pathophysiol Haemost Thromb. 2006;35(1-2):103-10 PMID: 16855354
  140. Fenofibrate represses interleukin-17 and interferon-gamma expression and improves colitis in interleukin-10-deficient mice.
    Gastroenterology. 2007 Jul;133(1):108-23 PMID: 17631136
  141. Effect of different levels of omega-3 and omega-6 fatty acids on azoxymethane-induced colon carcinogenesis in F344 rats.
    Cancer Res. 1988 Dec 1;48(23):6642-7 PMID: 3180073
  142. Suppression of tumorigenesis in the Apc(min) mouse: down-regulation of beta-catenin signaling by a combination of tea plus sulindac.
    Carcinogenesis. 2003 Feb;24(2):263-7 PMID: 12584176
  143. Characterization of colonic polyps by two-dimensional gel electrophoresis.
    Electrophoresis. 1999 Apr-May;20(4-5):1055-64 PMID: 10344285
  144. PPARbeta/delta regulates paneth cell differentiation via controlling the hedgehog signaling pathway.
    Gastroenterology. 2006 Aug;131(2):538-53 PMID: 16890607
  145. Components of olive oil and chemoprevention of colorectal cancer.
    Nutr Rev. 2005 Nov;63(11):374-86 PMID: 16370222
  146. Novel selective small molecule agonists for peroxisome proliferator-activated receptor delta (PPARdelta)--synthesis and biological activity.
    Bioorg Med Chem Lett. 2003 May 5;13(9):1517-21 PMID: 12699745
  147. RNA interference against peroxisome proliferator-activated receptor delta gene promotes proliferation of human colorectal cancer cells.
    Dis Colon Rectum. 2008 Mar;51(3):318-26; discussion 326-8 PMID: 18214615
  148. Differential regulation and properties of angiopoietin-like proteins 3 and 4.
    J Lipid Res. 2005 Jul;46(7):1484-90 PMID: 15863837
  149. Stromal production of prostacyclin confers an antiapoptotic effect to colonic epithelial cells.
    Cancer Res. 2003 Apr 15;63(8):1748-51 PMID: 12702555
  150. Angiopoietin-like 4 prevents metastasis through inhibition of vascular permeability and tumor cell motility and invasiveness.
    Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18721-6 PMID: 17130448
  151. Colorectal cancers in a new mouse model of familial adenomatous polyposis: influence of genetic and environmental modifiers.
    Lab Invest. 2004 Dec;84(12):1619-30 PMID: 15502862
  152. 9-cis-retinoic acid enhances fatty acid-induced expression of the liver fatty acid-binding protein gene.
    FEBS Lett. 1997 Aug 4;412(3):480-4 PMID: 9276450
  153. Promotion of colon tumors in C57BL/6J-APC(min)/+ mice by thiazolidinedione PPARgamma agonists and a structurally unrelated PPARgamma agonist.
    Toxicol Pathol. 2004 Jan-Feb;32(1):58-63 PMID: 14713549
  154. Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) ligands do not potentiate growth of human cancer cell lines.
    Carcinogenesis. 2007 Dec;28(12):2641-9 PMID: 17693664
  155. The Min (multiple intestinal neoplasia) mutation: its effect on gut epithelial cell differentiation and interaction with a modifier system.
    J Cell Biol. 1992 Mar;116(6):1517-26 PMID: 1541640
  156. Aspirin-induced apoptosis in jurkat cells is not mediated by peroxisome proliferator-activated receptor delta.
    Mol Cell Biochem. 2004 Nov;266(1-2):57-63 PMID: 15646027
  157. Ligand activation of peroxisome proliferator-activated receptor-beta/delta(PPARbeta/delta) inhibits cell growth of human N/TERT-1 keratinocytes.
    Cell Signal. 2007 Jun;19(6):1163-71 PMID: 17254750
  158. Dietary fatty acids and colorectal cancer: a case-control study.
    Am J Epidemiol. 2007 Jul 15;166(2):181-95 PMID: 17493949
  159. Genetic identification of Mom-1, a major modifier locus affecting Min-induced intestinal neoplasia in the mouse.
    Cell. 1993 Nov 19;75(4):631-9 PMID: 8242739
  160. Prostacyclin: a potent antimetastatic agent.
    Science. 1981 Jun 12;212(4500):1270-2 PMID: 7015512
  161. PPARgamma and PPARdelta negatively regulate specific subsets of lipopolysaccharide and IFN-gamma target genes in macrophages.
    Proc Natl Acad Sci U S A. 2003 May 27;100(11):6712-7 PMID: 12740443
  162. Concomitant suppression of hyperlipidemia and intestinal polyp formation by increasing lipoprotein lipase activity in Apc-deficient mice.
    Biol Chem. 2006 Apr;387(4):381-5 PMID: 16606335
  163. Modulation of keratinocyte gene expression and differentiation by PPAR-selective ligands and tetradecylthioacetic acid.
    J Invest Dermatol. 2001 May;116(5):702-12 PMID: 11348458
  164. Identification of c-MYC as a target of the APC pathway.
    Science. 1998 Sep 4;281(5382):1509-12 PMID: 9727977
  165. Peroxisome proliferator-activated receptor-beta/delta protects against chemically induced liver toxicity in mice.
    Hepatology. 2008 Jan;47(1):225-35 PMID: 18038451
  166. Tissue and cell-specific patterns of expression of rat liver and intestinal fatty acid binding protein during development and in experimental colonic and small intestinal adenocarcinomas.
    Lab Invest. 1993 Jun;68(6):663-75 PMID: 8515653
  167. Modulation of mitogenesis by liver fatty acid binding protein.
    Cancer Metastasis Rev. 1994 Dec;13(3-4):317-36 PMID: 7712594
  168. Regulatory functions of PPARbeta in metabolism: implications for the treatment of metabolic syndrome.
    Biochim Biophys Acta. 2007 Aug;1771(8):983-90 PMID: 17392020
  169. No evidence that polymorphisms in CYP2C8, CYP2C9, UGT1A6, PPARdelta and PPARgamma act as modifiers of the protective effect of regular NSAID use on the risk of colorectal carcinoma.
    Pharmacogenet Genomics. 2005 Oct;15(10):713-21 PMID: 16141797
  170. Peroxisome proliferator-activated receptor-delta attenuates colon carcinogenesis.
    Nat Med. 2004 May;10(5):481-3 PMID: 15048110
  171. Differentiation of trophoblast giant cells and their metabolic functions are dependent on peroxisome proliferator-activated receptor beta/delta.
    Mol Cell Biol. 2006 Apr;26(8):3266-81 PMID: 16581799
  172. The PPARdelta agonist GW501516 suppresses interleukin-6-mediated hepatocyte acute phase reaction via STAT3 inhibition.
    Eur J Clin Invest. 2007 May;37(5):425-33 PMID: 17461989
  173. Potential role for peroxisome proliferator activated receptor (PPAR) in preventing colon cancer.
    Gut. 2003 Sep;52(9):1317-22 PMID: 12912864
  174. Peroxisome proliferator-activated receptors (PPARs) and associated transcription factors in colon cancer: reduced expression of PPARgamma-coactivator 1 (PGC-1).
    Cancer Lett. 2004 Jan 8;203(1):25-33 PMID: 14670614
  175. The peroxisome proliferator-activated receptor delta, an integrator of transcriptional repression and nuclear receptor signaling.
    Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2613-8 PMID: 11867749
  176. Activation of nuclear hormone receptor peroxisome proliferator-activated receptor-delta accelerates intestinal adenoma growth.
    Nat Med. 2004 Mar;10(3):245-7 PMID: 14758356
  177. Peroxisome proliferator-activated receptor gamma agonist troglitazone induces colon tumors in normal C57BL/6J mice and enhances colonic carcinogenesis in Apc1638 N/+ Mlh1+/- double mutant mice.
    Int J Cancer. 2005 Sep 10;116(4):495-9 PMID: 15818612
  178. Differential activation of peroxisome proliferator-activated receptors by eicosanoids.
    J Biol Chem. 1995 Oct 13;270(41):23975-83 PMID: 7592593
  179. Activation of PPAR gamma and delta by conjugated linoleic acid mediates protection from experimental inflammatory bowel disease.
    Gastroenterology. 2004 Sep;127(3):777-91 PMID: 15362034
Article Info
Journal
Clinical science (London, England : 1979)
Abbr.
Clin Sci (Lond)
ISSN
1470-8736
DOI
10.1042/CS20080022
Email
[email protected]
Published
2008-08-00
Pages
107-27
Language
English
Region
England
NLM ID
7905731
PMCID
PMC2705117
Subset
IM
Grants
NCI NIH HHS · R01 CA097999 · United States
NCI NIH HHS · R01 CA124533 · United States
Intramural NIH HHS · Z01 BC005708-16 · United States
NCI NIH HHS · R01 CA97999 · United States
External Links
PubMed source DOI: 10.1042/CS20080022 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2