Advertisement

Regulation of Squamous Cell Carcinoma Carcinogenesis by Peroxisome Proliferator-Activated Receptors

  • Jeffrey M. Peters
  • Frank J. Gonzalez
Chapter

Abstract

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that respond to endogenous and exogenous signaling molecules and modulate cellular functions. PPARs regulate many target genes that in turn influence cell growth, differentiation, and inflammatory signaling. These changes can occur through direct transcriptional up-regulation of target genes, through secondary changes subsequent to direct transcriptional up-regulation of target genes, and through protein-protein interactions. The focus of this chapter is to summarize PPAR-dependent regulation of cellular signaling in squamous epithelium, and how these changes influence cancer.

Keywords

Conjugate Linoleic Acid Terminal Differentiation Ligand Activation Skin Tumorigenesis Terminal Differentiation Marker 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Ali FY, Egan K, Fitzgerald GA et al. (2005) Role of prostacyclin receptor versus PPARβ with treprostinil sodium on lung fibroblast proliferation. Am J Respir Cell Mol Biol 34:242–246PubMedCrossRefGoogle Scholar
  2. Arsenijevic D, de Bilbao F, Plamondon J et al. (2006) Increased infarct size and lack of hyperphagic response after focal cerebral ischemia in peroxisome proliferator-activated receptor β-deficient mice. J Cereb Blood Flow Metab 26:433–445PubMedCrossRefGoogle Scholar
  3. Aung CS, Faddy HM, Lister EJ et al. (2006) Isoform specific changes in PPARα and β in colon and breast cancer with differentiation. Biochem Biophys Res Commun 340:656–660PubMedCrossRefGoogle Scholar
  4. Barish GD, Atkins AR, Downes M et al. (2008) PPARδ regulates multiple proinflammatory pathways to suppress atherosclerosis. Proc Natl Acad Sci USA 105:4271–4276PubMedCrossRefGoogle Scholar
  5. Bassaganya-Riera J, Reynolds K, Martino-Catt S et al. (2004) Activation of PPARγ and δ by conjugated linoleic acid mediates protection from experimental inflammatory bowel disease. Gastroenterology 127:777–791PubMedCrossRefGoogle Scholar
  6. Bility MT, Devlin-Durante MK, Blazanin N et al. (2008) Ligand activation of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) inhibits chemically-induced skin tumorigenesis. Carcinogenesis 29:2406–2414PubMedCrossRefGoogle Scholar
  7. Borland MG, Foreman JE, Girroir EE et al. (2008) Ligand activation of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) inhibits cell proliferation in human HaCaT keratinocytes. Mol Pharmacol 74:1429–1442PubMedCrossRefGoogle Scholar
  8. Burdick AD, Kim DJ, Peraza MA et al. (2006) The role of peroxisome proliferator-activated receptor-β/δ in epithelial cell growth and differentiation. Cell Signal 18:9–20PubMedCrossRefGoogle Scholar
  9. Burdick AD, Bility MT, Girroir EE et al. (2007) Ligand activation of peroxisome proliferator-­activated receptor-β/δ (PPARβ/δ) inhibits cell growth of human N/TERT-1 keratinocytes. Cell Signal 19:1163–1171PubMedCrossRefGoogle Scholar
  10. Chawla A, Lee CH, Barak Y et al. (2003) PPARδ is a very low-density lipoprotein sensor in macrophages. Proc Natl Acad Sci USA 100:1268–1273PubMedCrossRefGoogle Scholar
  11. Delerive P, De Bosscher K, Besnard S et al. (1999) Peroxisome proliferator-activated receptor α negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappaB and AP-1. J Biol Chem 274:32048–32054PubMedCrossRefGoogle Scholar
  12. Demerjian M, Man MQ, Choi EH et al. (2006) Topical treatment with thiazolidinediones, activators of peroxisome proliferator-activated receptor-gamma, normalizes epidermal homeostasis in a murine hyperproliferative disease model. Exp Dermatol 15:154–160PubMedCrossRefGoogle Scholar
  13. Di Loreto S, D’Angelo B, D’Amico MA et al. (2007) PPARβ agonists trigger neuronal differentiation in the human neuroblastoma cell line SH-SY5Y. J Cell Physiol 211:837–847PubMedCrossRefGoogle Scholar
  14. Ding G, Cheng L, Qin Q et al. (2006) PPARδ modulates lipopolysaccharide-induced TNFα inflammation signaling in cultured cardiomyocytes. J Mol Cell Cardiol 40:821–828PubMedCrossRefGoogle Scholar
  15. Dyroy E, Rost TH, Pettersen RJ et al. (2007) Tetradecylselenoacetic acid, a PPAR ligand with antioxidant, antiinflammatory, and hypolipidemic properties. Arterioscler Thromb Vasc Biol 27:628–634PubMedCrossRefGoogle Scholar
  16. Ellis CN, Varani J, Fisher GJ et al. (2000) Troglitazone improves psoriasis and normalizes models of proliferative skin disease: ligands for peroxisome proliferator-activated receptor-gamma inhibit keratinocyte proliferation. Arch Dermatol 136:609–616PubMedCrossRefGoogle Scholar
  17. Fan Y, Wang Y, Tang Z et al. (2008) Suppression of pro-inflammatory adhesion molecules by PPAR-δ in human vascular endothelial cells. Arterioscler Thromb Vasc Biol 28:315–321PubMedCrossRefGoogle Scholar
  18. Foreman JE, Sorg JM, McGinnis KS et al. (2009) Regulation of peroxisome proliferator-activated receptor-β/δ by the APC/β-CATENIN pathway and nonsteroidal anti-inflammatory drugs. Mol Carcinog. doi:10.1002/mc.20546PubMedGoogle Scholar
  19. Forman BM, Chen J, Evans RM (1997) Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors α and δ. Proc Natl Acad Sci USA 94:4312–4317PubMedCrossRefGoogle Scholar
  20. Fukumoto K, Yano Y, Virgona N et al. (2005) Peroxisome proliferator-activated receptor delta as a molecular target to regulate lung cancer cell growth. FEBS Lett 579:3829–3836PubMedCrossRefGoogle Scholar
  21. Girroir EE, Hollingshead HE, Billin AN et al. (2008a) Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) ligands inhibit growth of UACC903 and MCF7 human cancer cell lines. Toxicology 243:236–243PubMedCrossRefGoogle Scholar
  22. Girroir EE, Hollingshead HE, He P et al. (2008b) Quantitative expression patterns of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) protein in mice. Biochem Biophys Res Commun 371:456–461PubMedCrossRefGoogle Scholar
  23. Graham TL, Mookherjee C, Suckling KE et al. (2005) The PPARδ agonist GW0742X reduces atherosclerosis in LDLR-/- mice. Atherosclerosis 181:29–37PubMedCrossRefGoogle Scholar
  24. Hanley K et al. (1997) Activators of the nuclear hormone receptors PPARalpha and FXR accelerate the development of the fetal epidermal permeability barrier. J Clin Invest 100:705–712PubMedCrossRefGoogle Scholar
  25. Hanley K, Jiang Y, He SS et al. (1998) Keratinocyte differentiation is stimulated by activators of the nuclear hormone receptor PPARα. J Invest Dermatol 110:368–375PubMedCrossRefGoogle Scholar
  26. Harris G, Ghazallah RA, Nascene D et al. (2005) PPAR activation and decreased proliferation in oral carcinoma cells with 4-HPR. Otolaryngol Head Neck Surg 133:695–701PubMedCrossRefGoogle Scholar
  27. Hashimoto Y, Shimada Y, Itami A et al. (2003) Growth inhibition through activation of peroxisome proliferator-activated receptor gamma in human oesophageal squamous cell carcinoma. Eur J Cancer 39:2239–2246PubMedCrossRefGoogle Scholar
  28. Haskova Z, Hoang B, Luo G et al. (2008) Modulation of LPS-induced pulmonary neutrophil infiltration and cytokine production by the selective PPARβ/δ ligand GW0742. Inflamm Res 57:314–321PubMedCrossRefGoogle Scholar
  29. He G, Thuillier P, Fischer SM (2004) Troglitazone inhibits cyclin D1 expression and cell cycling independently of PPARγ in normal mouse skin keratinocytes. J Invest Dermatol 123:1110–1119PubMedCrossRefGoogle Scholar
  30. He G, Muga S, Thuillier P et al. (2005) The effect of PPARγ ligands on UV- or chemically-induced carcinogenesis in mouse skin. Mol Carcinog 43:198–206PubMedCrossRefGoogle Scholar
  31. Hollingshead HE, Killins RL, Borland MG et al. (2007a) Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) ligands do not potentiate growth of human cancer cell lines. Carcinogenesis 28:2641–2649PubMedCrossRefGoogle Scholar
  32. Hollingshead HE, Morimura K, Adachi M et al. (2007b) PPARβ/δ protects against experimental colitis through a ligand-independent mechanism. Dig Dis Sci 52:2912–2919PubMedCrossRefGoogle Scholar
  33. Hollingshead HE, Borland MG, Billin AN et al. (2008) Ligand activation of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) and inhibition of cyclooxygenase 2 (COX2) attenuate colon carcinogenesis through independent signaling mechanisms. Carcinogenesis 29:169–176PubMedCrossRefGoogle Scholar
  34. Hong C, Tontonoz P (2008) Coordination of inflammation and metabolism by PPAR and LXR nuclear receptors. Curr Opin Genet Dev 18:461–467PubMedCrossRefGoogle Scholar
  35. Indra AK, Castaneda E, Antal MC et al. (2007) Malignant transformation of DMBA/TPA-induced papillomas and nevi in the skin of mice selectively lacking retinoid-X-receptor α in epidermal keratinocytes. J Invest Dermatol 127:1250–1260PubMedCrossRefGoogle Scholar
  36. Jaeckel EC, Raja S, Tan J et al. (2001) Correlation of expression of cyclooxygenase-2, vascular endothelial growth factor, and peroxisome proliferator-activated receptor delta with head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 127:1253–1259PubMedGoogle Scholar
  37. Jakobsen MA, Petersen RK, Kristiansen K et al. (2006) Peroxisome proliferator-activated receptor α, δ, 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 63:330–337PubMedCrossRefGoogle Scholar
  38. Kang K, Reilly SM, Karabacak V et al. (2008) Adipocyte-derived Th2 cytokines and myeloid PPARδ regulate macrophage polarization and insulin sensitivity. Cell Metab 7:485–495PubMedCrossRefGoogle Scholar
  39. Kilgore KS, Billin AN (2008) PPARβ/δ ligands as modulators of the inflammatory response. Curr Opin Investig Drugs 9:463–469PubMedGoogle Scholar
  40. Kim DJ, Akiyama TE, Harman FS et al. (2004) Peroxisome proliferator-activated receptor beta (delta)-dependent regulation of ubiquitin C expression contributes to attenuation of skin ­carcinogenesis. J Biol Chem 279:23719–23727PubMedCrossRefGoogle Scholar
  41. Kim DJ, Murray IA, Burns AM et al. (2005) Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) inhibits epidermal cell proliferation by down-regulation of kinase activity. J Biol Chem 280:9519–9527PubMedCrossRefGoogle Scholar
  42. Kim DJ, Bility MT, Billin AN et al. (2006) PPARβ/δ selectively induces differentiation and inhibits cell proliferation. Cell Death Differ 13:53–60PubMedCrossRefGoogle Scholar
  43. Kim HJ, Ham SA, Kim SU et al. (2008) Transforming growth factor-beta1 is a molecular target for the peroxisome proliferator-activated receptor delta. Circ Res 102:193–200PubMedCrossRefGoogle Scholar
  44. Kino T, Rice KC, Chrousos GP (2007) The PPARδ agonist GW501516 suppresses interleukin-6-mediated hepatocyte acute phase reaction via STAT3 inhibition. Eur J Clin Invest 37:425–433PubMedCrossRefGoogle Scholar
  45. Kippenberger S, Loitsch SM, Grundmann-Kollmann M et al. (2001) Activators of peroxisome proliferator-activated receptors protect human skin from ultraviolet-B-light-induced inflammation. J Invest Dermatol 117:1430–1436PubMedCrossRefGoogle Scholar
  46. Knutsen GL, Kovatch RM, Robinson M (1986) Gross and microscopic lesions in the female SENCAR mouse skin and lung in tumor initiation and promotion studies. Environ Health Perspect 68:91–104PubMedCrossRefGoogle Scholar
  47. Komuves LG et al. (1998) Ligands and activators of nuclear hormone receptors regulate epidermal differentiation during fetal rat skin development. J Invest Dermatol 111:429–433PubMedCrossRefGoogle Scholar
  48. Komuves LG, Hanley K, Lefebvre AM et al. (2000) Stimulation of PPARα promotes epidermal keratinocyte differentiation in vivo. J Invest Dermatol 115:353–360PubMedCrossRefGoogle Scholar
  49. Lim HJ, Lee S, Park JH et al. (2009) PPARδ agonist L-165041 inhibits rat vascular smooth muscle cell proliferation and migration via inhibition of cell cycle. Atherosclerosis 202:446–454PubMedCrossRefGoogle Scholar
  50. Man MQ, Barish GD, Schmuth M et al. (2007) Deficiency of PPARβ/δ in the epidermis results in defective cutaneous permeability barrier homeostasis and increased inflammation. J Invest Dermatol 128:370–377PubMedGoogle Scholar
  51. Mao-Qiang M, Fowler AJ, Schmuth M et al. (2004) Peroxisome-proliferator-activated receptor (PPAR)-gamma activation stimulates keratinocyte differentiation. J Invest Dermatol 123:305–312PubMedCrossRefGoogle Scholar
  52. Marathe C, Bradley MN, Hong C et al. (2008) Preserved glucose tolerance in high fat diet-fed C57BL/6 mice transplanted with PPARγ −/−, PPARδ −/−, PPARγ δ −/− or LXRalpha β −/− bone marrow. J Lipid Res. doi:10.1194/jlr.M800189-JLR200PubMedGoogle Scholar
  53. Marin HE, Peraza MA, Billin AN et al. (2006) Ligand activation of peroxisome proliferator-activated receptor β/δ (PPARβ/δ) inhibits colon carcinogenesis. Cancer Res 66:4394–4401PubMedCrossRefGoogle Scholar
  54. Martinasso G, Maggiora M, Trombetta A et al. (2006) 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 69:353–365PubMedCrossRefGoogle Scholar
  55. Masuda T, Wada K, Nakajima A et al. (2005) Critical role of peroxisome proliferator-activated receptor gamma on anoikis and invasion of squamous cell carcinoma. Clin Cancer Res 11:4012–4021PubMedCrossRefGoogle Scholar
  56. Matsuura H, Adachi H, Smart RC et al. (1999) Correlation between expression of peroxisome proliferator-activated receptor beta and squamous differentiation in epidermal and tracheobronchial epithelial cells. Mol Cell Endocrinol 147:85–92PubMedCrossRefGoogle Scholar
  57. Matthiessen MW, Pedersen G, Albrektsen T et al. (2005) Peroxisome proliferator-activated receptor expression and activation in normal human colonic epithelial cells and tubular adenomas. Scand J Gastroenterol 40:198–205PubMedCrossRefGoogle Scholar
  58. Michalik L, Desvergne B, Tan NS et al. (2001) Impaired skin wound healing in peroxisome ­proliferator-activated receptor (PPAR)α and PPARβ mutant mice. J Cell Biol 154:799–814PubMedCrossRefGoogle Scholar
  59. Müller-Brüsselbach S, Kömhoff M, Rieck M et al. (2007) Deregulation of tumor angiogenesis and blockade of tumor growth in PPARβ-deficient mice. EMBO J 26:3686–3698PubMedCrossRefGoogle Scholar
  60. Nadra K, Anghel SI, Joye E et al. (2006) Differentiation of trophoblast giant cells and their metabolic functions are dependent on peroxisome proliferator-activated receptor β/δ. Mol Cell Biol 26:3266–3281PubMedCrossRefGoogle Scholar
  61. Nagasawa T, Inada Y, Nakano S et al. (2006) Effects of bezafibrate, PPAR pan-agonist, and GW501516, PPARδ agonist, on development of steatohepatitis in mice fed a methionine- and choline-deficient diet. Eur J Pharmacol 536:182–191PubMedCrossRefGoogle Scholar
  62. Nakashiro K, Begum NM, Uchida D et al. (2003) Thiazolidinediones inhibit cell growth of human oral squamous cell carcinoma in vitro independent of peroxisome proliferator-activated receptor gamma. Oral Oncol 39:855–861PubMedCrossRefGoogle Scholar
  63. Nicol CJ, Yoon M, Ward JM et al. (2004) PPARγ influences susceptibility to DMBA-induced mammary, ovarian and skin carcinogenesis. Carcinogenesis 25:1747–1755PubMedCrossRefGoogle Scholar
  64. Nijsten T, Geluyckens E, Colpaert C et al. (2005) Peroxisome proliferator-activated receptors in squamous cell carcinoma and its precursors. J Cutan Pathol 32:340–347PubMedCrossRefGoogle Scholar
  65. Nikitakis NG, Siavash H, Hebert C et al. (2002) 15-PGJ2, but not thiazolidinediones, inhibits cell growth, induces apoptosis, and causes downregulation of Stat3 in human oral SCCa cells. Br J Cancer 87:1396–1403PubMedCrossRefGoogle Scholar
  66. Odegaard JI, Ricardo-Gonzalez RR, Red Eagle A et al. (2008) Alternative M2 activation of Kupffer cells by PPARδ ameliorates obesity-induced insulin resistance. Cell Metab 7:496–507PubMedCrossRefGoogle Scholar
  67. Ondrey F (2009) Peroxisome proliferator-activated receptor gamma pathway targeting in carcinogenesis: implications for chemoprevention. Clin Cancer Res 15:2–8PubMedCrossRefGoogle Scholar
  68. Otsuyama KI, Ma Z, Abroun S et al. (2007) PPARβ-mediated growth suppression of baicalein and dexamethasone in human myeloma cells. Leukemia 21:187–190PubMedCrossRefGoogle Scholar
  69. Ouyang N, Williams JL, Rigas B (2006) NO-donating aspirin isomers downregulate peroxisome proliferator-activated receptor (PPAR)δ expression in APC(min/+) mice proportionally to their tumor inhibitory effect: Implications for the role of PPARδ in carcinogenesis. Carcinogenesis 27:232–239PubMedCrossRefGoogle Scholar
  70. Pascual G, Fong AL, Ogawa S et al. (2005) A SUMOylation-dependent pathway mediates ­transrepression of inflammatory response genes by PPAR-gamma. Nature 437:759–763PubMedCrossRefGoogle Scholar
  71. Peraza MA, Burdick AD, Marin HE et al. (2006) The toxicology of ligands for peroxisome ­proliferator-activated receptors (PPAR). Toxicol Sci 90:269–295PubMedCrossRefGoogle Scholar
  72. Peters JM, Lee SST, Li W et al. (2000) Growth, adipose, brain and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor β/δ. Mol Cell Biol 20:5119–5128PubMedCrossRefGoogle Scholar
  73. Peters JM, Cheung C, Gonzalez FJ (2005) Peroxisome proliferator-activated receptor-α and liver cancer: where do we stand? J Mol Med 83:774–785PubMedCrossRefGoogle Scholar
  74. Peters JM, Hollingshead HE, Gonzalez FJ (2008) Role of peroxisome-proliferator-activated receptor β/δ (PPARβ/δ) in gastrointestinal tract function and disease. Clin Sci (Lond) 115:107–127CrossRefGoogle Scholar
  75. Planavila A, Rodriguez-Calvo R, Jove M et al. (2005) Peroxisome proliferator-activated receptor β/δ activation inhibits hypertrophy in neonatal rat cardiomyocytes. Cardiovasc Res 65:832–841PubMedCrossRefGoogle Scholar
  76. Polak PE, Kalinin S, Dello Russo C et al. (2005) Protective effects of a peroxisome proliferator-activated receptor-β/δ agonist in experimental autoimmune encephalomyelitis. J Neuroimmunol 168:65–75PubMedCrossRefGoogle Scholar
  77. Ravaux L, Denoyelle C, Monne C et al. (2007) Inhibition of interleukin-1β-induced group IIA secretory phospholipase A2 expression by peroxisome proliferator-activated receptors (PPARs) in rat vascular smooth muscle cells: cooperation between PPARβ and the proto-oncogene BCL-6. Mol Cell Biol 27:8374–8387PubMedCrossRefGoogle Scholar
  78. Riserus U, Sprecher D, Johnson T et al. (2008) Activation of peroxisome proliferator-activated receptor (PPAR)δ promotes reversal of multiple metabolic abnormalities, reduces oxidative stress, and increases fatty acid oxidation in moderately obese men. Diabetes 57:332–339PubMedCrossRefGoogle Scholar
  79. Rival Y, Beneteau N, Taillandier T et al. (2002) PPARα and PPARδ activators inhibit cytokine-induced nuclear translocation of NF-kappaB and expression of VCAM-1 in EAhy926 endothelial cells. Eur J Pharmacol 435:143–151PubMedCrossRefGoogle Scholar
  80. Rival Y, Puech L, Taillandier T et al. (2009) PPAR activators and COX inhibitors selectively block cytokine-induced COX-2 expression and activity in human aortic smooth muscle cells. Eur J Pharmacol 606:121–129PubMedCrossRefGoogle Scholar
  81. Rivier M, Safonova I, Lebrun P et al. (1998) Differential expression of peroxisome proliferator-activated receptor subtypes during the differentiation of human keratinocytes. J Invest Dermatol 111:1116–1121PubMedCrossRefGoogle Scholar
  82. Rodriguez-Calvo R, Serrano L, Coll T et al. (2008) Activation of peroxisome proliferator-­activated receptor β/δ (PPARβ/δ) inhibits LPS-induced cytokine production in adipocytes by lowering NF-{kappa}B activity via ERK1/2. Diabetes 57:2149–2157PubMedCrossRefGoogle Scholar
  83. Rumi MA, Sato H, Ishihara S et al. (2002) Growth inhibition of esophageal squamous carcinoma cells by peroxisome proliferator-activated receptor-gamma ligands. J Lab Clin Med 140:17–26PubMedCrossRefGoogle Scholar
  84. Saluja I, Granneman JG, Skoff RP (2001) PPARδ agonists stimulate oligodendrocyte differentiation in tissue culture. Glia 33:191–204PubMedCrossRefGoogle Scholar
  85. Schmuth M, Haqq CM, Cairns WJ et al. (2004) Peroxisome proliferator-activated receptor (PPAR)-β/δ stimulates differentiation and lipid accumulation in keratinocytes. J Invest Dermatol 122:971–983PubMedCrossRefGoogle Scholar
  86. Sertznig P, Seifert M, Tilgen W et al. (2008) Cross-regulation of peroxisome proliferator-activated receptor- (PPAR) and vitamin D receptor-signaling pathways in melanoma cells. Exp Dermatol 17:626–627CrossRefGoogle Scholar
  87. Shan W, Nicol CJ, Ito S et al. (2008a) Peroxisome proliferator-activated receptor-β/δ protects against chemically induced liver toxicity in mice. Hepatology 47:225–235PubMedCrossRefGoogle Scholar
  88. Shan W, Palkar PS, Murray IA et al. (2008b) Ligand activation of peroxisome proliferator-activated receptor β/δ (PPARβ/δ) attenuates carbon tetrachloride hepatotoxicity by downregulating proinflammatory gene expression. Toxicol Sci 105:418–428PubMedCrossRefGoogle Scholar
  89. Sheng L, Ye P, Liu YX et al. (2008) Peroxisome proliferator-activated receptor β/δ activation improves angiotensin II-induced cardiac hypertrophy in vitro. Clin Exp Hypertens 30:109–119PubMedCrossRefGoogle Scholar
  90. Smeets PJ, Teunissen BE, Planavila A et al. (2008) Inflammatory pathways are activated during cardiomyocyte hypertrophy and attenuated by PPARα and PPARδ. J Biol Chem 283:29109–29118PubMedCrossRefGoogle Scholar
  91. Spiegelman BM et al. (1997) PPAR gamma and the control of adipogenesis. Biochimie 79:111–112, ReviewPubMedCrossRefGoogle Scholar
  92. Staumont-Salle D, Abboud G, Brenuchon C et al. (2008) Peroxisome proliferator-activated ­receptor α regulates skin inflammation and humoral response in atopic dermatitis. J Allergy Clin Immunol 121(962–968):e966Google Scholar
  93. Takata Y, Liu J, Yin F et al. (2008) PPARδ-mediated antiinflammatory mechanisms inhibit angiotensin II-accelerated atherosclerosis. Proc Natl Acad Sci USA 105:4277–4282PubMedCrossRefGoogle Scholar
  94. Tan NS, Michalik L, Noy N et al. (2001) Critical roles of PPARβ/δ in keratinocyte response to inflammation. Genes Dev 15:3263–3277PubMedCrossRefGoogle Scholar
  95. Terashita Y, Sasaki H, Haruki N et al. (2002) Decreased peroxisome proliferator-activated receptor gamma gene expression is correlated with poor prognosis in patients with esophageal cancer. Jpn J Clin Oncol 32:238–243PubMedCrossRefGoogle Scholar
  96. Teunissen BE, Smeets PJ, Willemsen PH et al. (2007) Activation of PPARδ inhibits cardiac fibroblast proliferation and the transdifferentiation into myofibroblasts. Cardiovasc Res 75:519–529PubMedCrossRefGoogle Scholar
  97. Thuillier P, Anchiraico GJ, Nickel KP et al. (2000) Activators of peroxisome proliferator-activated receptor-α partially inhibit mouse skin tumor promotion. Mol Carcinog 29:134–142PubMedCrossRefGoogle Scholar
  98. Varley CL, Stahlschmidt J, Smith B et al. (2004) Activation of peroxisome proliferator-activated receptor-gamma reverses squamous metaplasia and induces transitional differentiation in ­normal human urothelial cells. Am J Pathol 164:1789–1798PubMedGoogle Scholar
  99. Varnat F, Heggeler BB, Grisel P et al. (2006) PPARβ/δ regulates paneth cell differentiation via controlling the hedgehog signaling pathway. Gastroenterology 131:538–553PubMedCrossRefGoogle Scholar
  100. Vosper H, Khoudoli GA, Palmer CN (2003) The peroxisome proliferator activated receptor delta is required for the differentiation of THP-1 monocytic cells by phorbol ester. Nucl Recept 1:9PubMedCrossRefGoogle Scholar
  101. Welch JS, Ricote M, Akiyama TE et al. (2003) PPARγ and PPARδ negatively regulate specific subsets of lipopolysaccharide and IFN-gamma target genes in macrophages. Proc Natl Acad Sci USA 100:6712–6717PubMedCrossRefGoogle Scholar
  102. Werling U, Siehler S, Litfin M et al. (2001) Induction of differentiation in F9 cells and activation of peroxisome proliferator-activated receptor delta by valproic acid and its teratogenic derivatives. Mol Pharmacol 59:1269–1276PubMedGoogle Scholar
  103. Westergaard M, Henningsen J, Svendsen ML et al. (2001) Modulation of keratinocyte gene expression and differentiation by PPAR-selective ligands and tetradecylthioacetic acid. J Invest Dermatol 116:702–712PubMedCrossRefGoogle Scholar
  104. Woo CH, Massett MP, Shishido T et al. (2006) ERK5 activation inhibits inflammatory responses via peroxisome proliferator-activated receptor δ (PPARδ) stimulation. J Biol Chem 281:32164–32174PubMedCrossRefGoogle Scholar
  105. Yang L, Zhou ZG, Zheng XL et al. (2008) RNA interference against peroxisome proliferator-activated receptor delta gene promotes proliferation of human colorectal cancer cells. Dis Colon Rectum 51:318–328PubMedCrossRefGoogle Scholar
  106. Yoshida K, Hirose Y, Tanaka T et al. (2003) Inhibitory effects of troglitazone, a peroxisome ­proliferator-activated receptor gamma ligand, in rat tongue carcinogenesis initiated with 4-nitroquinoline 1-oxide. Cancer Sci 94:365–371PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Veterinary and Biomedical Sciences, The Center for Molecular Toxicology and CarcinogenesisThe Pennsylvania State UniversityUniversity ParkUSA

Personalised recommendations