Biomed. Papers 146(2), 11-14 (2002) | DOI: 10.5507/bp.2002.002

Peroxisome proliferator-activated receptors (PPARs) in health and disease.

Jiří Ehrmann Jr.a, Nicol Vavrušováa, Yrjo Collanb, Zdeněk Kolářa
a Department of Pathology, Laboratory of Molecular Pathology, Faculty of Medicine, Palacký University, Hněvotínská 3, Olomouc 77515, Czech Republic
b Department of Pathology, Faculty of Medicine, University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland

Peroxisome proliferator-activated receptors (PPARs) belong to the superfamily of steroid-thyroid-retinoid nuclear receptors. PPARs are transcription factors activated by specific ligands and play an important role during cell signalling. Intensive study of PPARs during recent years has revealed their importance in both normal physiology and in the pathology of various tissues. They participate in the regulation of lipid metabolism, inflammation and the development of atherosclerosis or diabetes. They also play a role in the regulation of growth and differentiation of cancer. It has been suggested that PPAR ligands may have potent anticancer effects and thereFirst may serve as potential anticancer drugs. In this review we focus on a role of PPARs in breast cancer and in glial tumors of the brain.

Keywords: Orphan receptors, PPARs, Inflammation, Atherosclerosis, Cancer

Received: September 10, 2002; Published: December 1, 2002  Show citation

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Ehrmann, J., Vavrušová, N., Collan, Y., & Kolář, Z. (2002). Peroxisome proliferator-activated receptors (PPARs) in health and disease. Biomedical papers146(2), 11-14. doi: 10.5507/bp.2002.002
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References

  1. Kumar R, Thompson EB (1999) The structure of the nuclear hormone receptors. Steroids 64, 310-319. Go to original source... Go to PubMed...
  2. Kliewer SA, Lehmann JM, Wilson TM (1999) Orphan nuclear receptors: shifting endocrinology into reverse. Science 284, 757-760. Go to original source... Go to PubMed...
  3. Heyman RA, Mangelsdorf DJ, Dyck JA, Stein RB, Eichele G, Evans RM, Thaller C (1992) 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell 68, 397-406. Go to original source... Go to PubMed...
  4. Sinal CJ, Tohkin M, Miyata M, Ward JM, Lambert G, Gonzales FJ (2000) Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell 102, 731-744. Go to original source... Go to PubMed...
  5. Isseman I, Green S (1990) Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347, 645-650. Go to original source... Go to PubMed...
  6. Corton JC, Anderson SP, Stauber A (2000) Central role of peroxisome proliferator-activated receptors in the actions of peroxisome proliferators. Annu. Rev. Pharmacol. Toxicol. 40, 491-518. Go to original source... Go to PubMed...
  7. Braissant O, Foufelle F, Scotto C, Dauca M, Wahli W (1996) Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR... Endocrinology 137, 354-366. Go to original source... Go to PubMed...
  8. Mansen A, Guardiola-Diaz H, Rafter J, Branting C, Gustafsson, JA (1996) Expression of the peroxisome proliferator-activated receptor (PPAR) in the mouse colonic mucosa. Biochem. Biophys. Res. Commun. 222, 844-851. Go to original source... Go to PubMed...
  9. Torra IP, Chinetti G, Duval C, Fruchart JC, Staels B (2001) Peroxisome proliferator-activated receptors: from transcriptional control to clinical practice. Curr. Opin. Lipidol. 12, 245-254. Go to original source...
  10. Peters JM, Rusyn I, Rose ML, Gonzales FJ, Thurman RG (2000) Peroxisome proliferator activated receptor alpha is restricted to hepatic parenchymal cells, not Kupffer cells: implications for the mechanism of action of peroxisome proliferators in hepatocarcinogenesis. Carcinogenesis 21, 823-826. Go to original source... Go to PubMed...
  11. Miller RT, Anderson SP, Corton JC, Cattley RC (2000) Apoptosis, mitosis and cyclophilin-40 expression in regressing peroxisome proliferator-induced adenomas. Carcinogenesis 21, 647-652. Go to original source... Go to PubMed...
  12. Li AC, Brown KK, Silvestre MJ, Willson TM, Palinski W, Glass CK (2001) Effects of PPAR ligands on atherosclerosis. Quiagen News 1, 14-16.
  13. Kersten S, Desvergne B, Wahli W (2000) Roles of PPARs in health and disease. Nature 405, 421-424. Go to original source... Go to PubMed...
  14. Everett L, Galli A, Crabb D (2000) The role of hepatic peroxisome proliferator-activated receptors (PPARs) in health and disease. Liver 20, 191-199. Go to original source... Go to PubMed...
  15. Murphy GJ, Holder JC (2000) PPAR-gamma agonists: therapeutic role in diabetes, inflammation and cancer. Trends Pharmacol. Sci. 21, 469-474. Go to original source...
  16. Ashby J, Brady A, Elcombe CR, Elliott BM, Ishmael J, Odum J, Tugwood JD, Kettle S, Purchase IF (1994) Mechanistically-based human hazard assessment of peroxisome proliferator-induced hepatocarcinogenesis. Hum. Exp. Toxicol. 13, Suppl. 2: S1-117. Go to original source... Go to PubMed...
  17. Moore KJ, Fitzgerald ML, Freeman MW (2001) Peroxisome proliferator-activated receptors in macrophage biology: friend or foe? Curr. Opin. Lipidol. 12, 519-527. Go to original source...
  18. Plutzky J (2001) Peroxisome proliferator-activated receptors in endothelial cell biology. Curr. Opin. Lipidol. 12, 511-518. Go to original source...
  19. Wakino S, Kintscher U, Liu Z, Kim S, Yin F, Ohba M, Kuroki T, Schonthal AH, Hsueh WA, Law RE (2001) PPAR gamma ligands inhibit mitogenic induction of p21Cip by modulating the PKC delta pathway in vascular smooth muscle cells. J. Biol. Chem. 276, 47650-47657. Go to original source... Go to PubMed...
  20. Chinetti G, Fruchart JC, Staels B (2001) Peroxisome proliferatoractivated receptors (PPARs): nuclear receptors with functions in the vascular wall. Z. Kardiol. 90, Suppl. 3, 125-132. Go to original source...
  21. Gale EAM (2001) Lessons from the glitazones: a story of drug development. Lancet 357, 1870-1875. Go to original source... Go to PubMed...
  22. Sarraf P, Mueller E, Smith WM, Wright HM, Kum JB, Aaltonen LA, de la Chapelle A, Spiegelman BM, Eng C (1999) Loss-offunction mutation in PPAR gamma associated with human colon cancer. Mol. Cell 3, 799-804. Go to original source...
  23. Patel L, Pass I, Coxon P, Downes CP, Smith SA, Macphee Ch (2001) Tumor suppresor and anti-inflammatory actions of PPAR gamma agonists are mediated via upregulation of PTEN. Curr. Biol. 11, 764-768. Go to original source... Go to PubMed...
  24. Samid D, Wells M, Greene ME, Shen W, Palmer CNA, Thibault, A. (2000) Peroxisome proliferator-activated receptor gamma as a novel target in cancer therapy: binding and activation by an aromatic fatty acid with clinical antitumor activity. Clin. Cancer Res. 6, 933-941.
  25. Brown PH, Lippman SM (2000) Chemoprevention of breast cancer. Breast Cancer Res. Treat. 62, 1-17. Go to original source...
  26. Roberts-Thompson SJ (2000) Peroxisome proliferator-activated receptors in tumorigenesis: targets of tumour promotion and treatment. Immunol. Cell Biol. 78, 436-441. Go to original source... Go to PubMed...
  27. Lippman SM, Lotan R (2000) Advances in the development of retinoids as chemopreventive agents. J. Nutr. 130, 479S-482S. Go to original source... Go to PubMed...
  28. Demetri GD, Fletcher CDM, Mueller E, Sarraf P, Naujoks R, Campbell N, Spiegelman BM, Singer S (1999) Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma. Proc. Natl. Acad. Sci. USA 96, 3950-3956. Go to original source... Go to PubMed...
  29. Ferrandina G, Melichar B, Loercher A, Verschraegen CF, Kudelka AP, Edwards CL, Scambia G, Kavanagh JJ, Abbruzzese JL, Freedman LS (1997) Growth inhibitory effects of sodium phenylacetate (NSC 3039) on ovarian carcinoma cells in vitro. Cancer Res. 57, 4309-4315.
  30. Rubin GL, Zhao Y, Kalus AM, Simpson ER. (2000) Peroxisome proliferator-activated receptor gamma ligands inhibit estrogen biosynthesis in human breast adipose tissue: possible implications for breast cancer therapy. Cancer Res. 60, 1604-1608.
  31. Mueller E, Sarraf P, Tontonoz P, Evans RM, Martin KJ, Zhang M, Fletcher C, Singer S, Spiegelman BM (1998) Terminal differentiation of human breast cancer through PPAR gamma. Mol. Cell 1, 465-470. Go to original source...
  32. Jiang WG, Redfern A, Bryce RP, Mansel RE (2000) Peroxisome proliferator activated receptor-gamma (PPAR-gamma) mediates the action of gamma linoleic acid in breast cancer cells. Prostaglandins Leukot. Essent. Fatty Acids 62, 119-127. Go to original source... Go to PubMed...
  33. Thoennes SR, Tate PL, Price TM, Kligore MW (2000) Differential transcriptional activation of peroxisome proliferator-activated receptor gamma by omega-3 and omega-6 fatty acids in MCF-7 cells. Mol. Cell Endocrinol. 160, 67-73. Go to original source... Go to PubMed...
  34. Collet GP, Betts AM, Johnson MI, Pulimood AB, Cook S, Neal DE, Robson CN (2000) Peroxisome proliferator-activated receptor alpha is an androgen-responsive gene in human prostate and is highly expressed in prostatic adenocarcinoma. Clin. Cancer Res. 6, 3241-3248.
  35. Butler R, Mitchell SH, Tindall DJ, Young CY (2000) Nonapoptotic cell death associated with S-phase arrest of prostate cancer cells via the peroxisome proliferator-activated receptor gamma ligand, 15-deoxy-delta12,14-prostaglandin J2. Cell Growth Differ. 11, 49-61.
  36. Kubota T, Koshizuka K, Williamson EA, Asou H, Said JW, Holden S, Miyoshi I, Koeffler HP (1998) Ligand for peroxisome proliferator-activated receptor gamma (troglitazone) has potent antitumor effect against human prostate cancer both in vitro and in vivo. Cancer Res. 58, 3344-3352.
  37. Guan YF, Zhang YH, Breyer RM, Davis L, Breyer MD (1999) Expression of peroxisome proliferator-activated receptor gamma (PPAR gamma) in human transitional bladder cancer and its role in inducing cell death. Neoplasia 1, 330-339. Go to original source... Go to PubMed...
  38. Padilla J, Kaur K, Harris SG, Phipps RP (2000) PPAR-gammamediated regulation of normal and malignant B lineage cells. Ann. N. Y. Acad. Sci. 905, 97-109. Go to original source... Go to PubMed...
  39. Hirase N, Yanase T, Mu Y, Muta K, Umemura T, Takayanagi R, Nawata H (2000) Thiazolidinedione suppresses the expression of erythroid phenotype in erythroleukemia cell line K562. Leuk. Res. 24, 393-400. Go to original source... Go to PubMed...
  40. Chang TH, Szabo E (2000) Induction of differentiation and apoptosis by ligands of peroxisome proliferator-activated receptor gamma in non-small cell lung cancer. Cancer Res. 60, 1129-1138.
  41. Sato H, Ishihara S, Kawashima K, Moriyama N, Suetsugu H, Kazumori H, Okuyama T, Rumi MA, Fukuda R, Nagasue N, Kinoshita Y (2000) Expression of peroxisome proliferator-activated receptor (PPAR)gamma in gastric cancer and inhibitory effects of PPARgamma agonists. Br. J. Cancer 83, 1394-1400. Go to original source... Go to PubMed...
  42. Gupta RA, Tan J, Krause WF, Geraci MW, Willson TM, Dey SK, DuBois RN (2000) Prostacyclin-mediated activation of peroxisome proliferator-activated receptor delta in colorectal cancer. Proc. Natl. Acad. Sci. USA 97, 13275-13280. Go to original source... Go to PubMed...
  43. Nwankwo JO, Robbins ME (2001) Peroxisome proliferator-activated receptor-gamma expression in human malignant and normal brain, breast and prostate-derived cells. Prostaglandins Leukot. Essent. Fatty Acids 64, 241-245. Go to original source... Go to PubMed...
  44. Chattopadhyay N, Singh DP, Heese O, Godbole MM, Sinohara T, Black PM, Brown EM (2000) Expression of peroxisome proliferator- activated receptors (PPARS) in human astrocytic cells: PPARgamma agonists as inducers of apoptosis. J. Neurosci. Res. 61, 67-74. Go to original source...
  45. Heneka MT, Feinstein DL, Galea E, Gleichmann M, Wullner U, Klockgether T (1999) Peroxisome proliferator-activated receptor gamma agonists protect cerebellar granule cells from cytokineinduced apoptotic cell death by inhibition of inducible nitric oxide synthase. J. Neuroimmunol. 100, 156-168. Go to original source...
  46. Heneka MT, Klockgether T, Feinstein DL (2000) Peroxisome proliferator-activated receptor-gamma ligands reduce neuronal inducible nitric oxide synthase expression and cell death in vivo. J. Neurosci. 20, 6862-6867. Go to original source... Go to PubMed...
  47. Zhou XP, Smith WM, Gimm O, Mueller E, Gao X, Sarraf P, Prior TW, Plass C, von Deimling A, Black PM, Yates AJ, Eng C (2000) Over-representation of PPAR gamma sequence variants in sporadic cases of glioblastoma multiforme: preliminary evidence for common low penetrance modifiers for brain tumour risk in the general population. J. Med. Genet. 37, 410-414. Go to original source... Go to PubMed...