Skip to main content

Advertisement

SpringerLink
Log in

Peroxisome proliferator-activated receptor γ (PPARγ) and colorectal carcinogenesis

  • Review
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) a member of the nuclear transcription factor superfamily is playing a role in colon carcinogenesis. Although not all in vivo models agree, PPARγ seems to have suppressive effects in this process favoring apoptosis and inhibiting the cell cycle by inducing expression of apoptosis and senescence proteins. With the recent discovery that anti-diabetic class of drugs thiazolidinediones act through activation of PPARγ, interest in this transcription factor has increased as it can now be pharmacologically activated in order to obtain tumor suppression. In addition, thiazolidinediones and other PPARγ agonists possess PPARγ-independent anti-tumor effects. Although PPARγ agonists may not by themselves be capable to induce clinical tumor regression, their combination with chemotherapy drugs or other targeted therapies is worth pursuing in the treatment of colorectal carcinoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Adams M, Reginato MJ, Shao D et al (1997) Transcriptional activation by peroxisome proliferators-activated receptor γ is inhibited by phosphorylation at a consensus mitogen-activated protein kinase site. J Biol Chem 272:5128–5132

    Article  PubMed  CAS  Google Scholar 

  • Allred CD, Kilgore MW (2005) Selective activation of PPARγ in breast, colon, and lung cancer cell lines. Mol Cell Endocrinol 235:21–29

    Article  PubMed  CAS  Google Scholar 

  • Altiok S, Xu M, Spiegelman BM (1997) PPARγ induces cell cycle withdrawal: inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A. Genes Dev 11:1987–1998

    Article  PubMed  CAS  Google Scholar 

  • Babbar N, Ignatenko NA, Casero Jr RA et al (2003) Cyclooxygenase-independent induction of apoptosis by sulindac sulfone is mediated by polyamines in colon cancer. J Biol Chem 278:47762–47775

    Article  PubMed  CAS  Google Scholar 

  • Baek SJ, Wilson LC, His LC et al (2003) Troglitazone, a Peroxisome Proliferator-activated receptor γ (PPARγ) ligand, selectively induces the early growth response-1 gene independently of PPARγ. J Biol Chem 278:5845–5853

    Article  PubMed  CAS  Google Scholar 

  • 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 127:777–791

    Article  PubMed  CAS  Google Scholar 

  • Bell-Parikh LC, Ide T, Lawson JA et al (2003) Biosynthesis of 15-deoxy-Δ12,14-PGJ2 and the ligation of PPARγ. J Clin Invest 112:945–955

    PubMed  CAS  Google Scholar 

  • Bogazzi F, Ultimieri F, Raggi F et al (2003) Changes in the expression of the peroxisome proliferator-activated receptor γ gene in the colonic polyps and colonic mucosa of acromegalic patients. J Clin Endocrinol Metab 88:3938–3942

    Article  PubMed  CAS  Google Scholar 

  • Bouancheau D, Buecher B, Jarry A et al (2005) The PPARγ K422Q mutation does not contribute to troglitazone inefficiency in colon cancer treatment. Cancer Lett 224:111–116

    PubMed  CAS  Google Scholar 

  • Boudjelal M, Wang Z, Voorhees JJ et al (2000) Ubiquitin/proteasome pathway regulates levels of retinoic acid receptor γ and retinoid X receptor α in human keratinocytes. Cancer Res 60:2247–2252

    PubMed  CAS  Google Scholar 

  • Bull AW, Steffensen KR, Leers J, Rafter JJ (2003) Activation of PPARγ in colon tumor cell lines by oxidized metabolites of linoleic acid, endogenous ligands for PPARγ. Carcinogenesis 24:1717–1722

    Article  PubMed  CAS  Google Scholar 

  • Camp HS, Tafuri SR (1997) Regulation of peroxisome proliferator-activated receptor γ activity by Mitogen-activated protein kinase. J Biol Chem 272:10811–10816

    Article  PubMed  CAS  Google Scholar 

  • Camp HS, Tafuri SR, Leff T (1999) c-Jun N-terminal kinase phosphorylates peroxisome proliferator-activated receptor-γ1 and negatively regulates its transcriptional activity. Endocrinology 140:392–397

    Article  PubMed  CAS  Google Scholar 

  • Chen F, Harrison LE (2005) Ciglitazone-induced cellular anti-proliferation oncreases p27kip1 protein levels through both increased transcriptional activity and inhibition of proteasome degradation. Cell Signaling 17:809–816

    Article  CAS  Google Scholar 

  • Chen ZY, Tseng C-C (2005) 15-Deoxy-Δ Prostaglandin J up-regulates Krüppel-like Factor 4 expression independently of peroxisome proliferator-activated receptor γ by activating the mitogen-activated protein kinase kinase/ extracellular signal-regulated kinase signal transduction pathway in HT-29 colon cancer cells. Mol Pharmacol 68:1203–1213

    Article  PubMed  CAS  Google Scholar 

  • Chen A, Xu J (2005) Activation of PPARγ by curcumin inhibits Moser cell growth and mediates suppression of cyclin D1 and EGFR. Am J Physiol Gastrointest Liver Physiol 288:G447–G456

    Article  PubMed  CAS  Google Scholar 

  • Chen GG, Lee JF, Wang SH et al (2002) Apoptosis induced by activation of peroxisome-proliferator activated receptor-gamma is associated with Bcl-2 and NF-kappa B in human colon cancer. Life Sci 70:2631–2646

    Article  PubMed  CAS  Google Scholar 

  • Chen GG, Xu H, Lee JFY et al (2003) 15-hydroxy-eicosatetraenoic acid arrests growth of colorectal cancer cells via a peroxisome proliferators-activated receptor gamma-dependent pathway. Int J Cancer 107:837–843

    Article  PubMed  CAS  Google Scholar 

  • Chintharlapalli S, Smith III R, Samudio I et al (2004) 1,1-Bis(3′-indolyl)-1-(p-substitutedphenyl)methanes induce peroxisome proliferator-activated receptor γ-mediated growth inhibition, transactivation, and differentiation markers in colon cancer cells. Cancer Res 64:5994–6001

    Article  PubMed  CAS  Google Scholar 

  • Chintharlapalli S, Papineni S, Baek SJ et al (2005) 1,1-Bis(3′-indolyl)-1-(p-substitutedphenyl)methanes are peroxisome proliferator-activated receptor γ agonists but decrease HCT-116 colon cancer cell survival through receptor-independent activation of early growth response-1 and nonsteroidal anti-inflammatory drug-activated gene-1. Mol Pharmacol 68:1782–1792

    PubMed  CAS  Google Scholar 

  • Cock T-A, Houten SM, Auwerx J (2004) Peroxisome proliferators-activated receptor-γ: too much of a good thing causes harm. EMBO Rep 5:142–147

    Article  PubMed  CAS  Google Scholar 

  • Cunard R, Ricote M, DiCampli D et al (2002) Regulation of cytokine expression by ligands of peroxisome proliferator activated receptors. J Immunol 168:2795–2802

    PubMed  CAS  Google Scholar 

  • Davies GF, Khandelwal RL, Roesler WJ (1999) Troglitazone induces expression of PPARγ in liver. Mol Cell Biol Res Commun 2:202–208

    Article  PubMed  CAS  Google Scholar 

  • Davies GF, Khandelwal RL, Wu L et al (2001) Inhibition of phosphoenolpyruvate carboxykinase (PEPCK) gene expression by troglitazone: a peroxisome proliferator-activated receptor-γ (PPARγ)-independent, antioxidant-related mechanism. Biochem Pharmacol 62:1071–1079

    Article  PubMed  CAS  Google Scholar 

  • Delerive P, Furman C, Teissier E et al (2000) Oxidized phospholipids activate PPARalpha in a phospholipase A2-dependent manner. FEBS Lett 471:34–38

    Article  PubMed  CAS  Google Scholar 

  • Demetri GD, Fletcher CDM, Mueller E et al (1999) Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-γ ligand troglitazone in patients with liposarcoma. Proc Natl Acad Sci 96:3951–3956

    Article  PubMed  CAS  Google Scholar 

  • DuBois RN, Gupta R, Brockman J et al (1998) The nuclear eicosanoid receptor, PPARγ, is aberrantly expressed in colonic cancers. Carcinogenesis 19:49–53

    Article  PubMed  CAS  Google Scholar 

  • Fajas L, Auboeuf D, Raspé E et al (1997) The organization, promoter analysis, and expression of the human PPARγ gene. J Biol Chem 272:18779–18789

    Article  PubMed  CAS  Google Scholar 

  • Fajas L, Fruchart J-C, Auwerx J (1998) PPARγ3 mRNA: a distinct PPARγ mRNA subtype transcribed from an independent promoter. FEBS Lett 438:55–60

    Article  PubMed  CAS  Google Scholar 

  • Fajas L, Egler V, Reiter R et al (2003) PPARγ controls cell proliferation and apoptosis in an RB-dependent manner. Oncogene 22:4186–4193

    Article  PubMed  CAS  Google Scholar 

  • Feilchenfeldt J, Bründler M-A, Soravia C et al (2004) Peroxisome proliferators-activated receptors (PPARs) and associated transcription factors in colon cancer: reduced expression of PPARγ-coactivator 1 (PGC-1). Cancer Lett 203:25–33

    Article  PubMed  CAS  Google Scholar 

  • Fodde R, Smits R, Clevers H (2001) APC, signal transduction and genetic instability in colorectal cancer. Nat Rev Cancer 1:55–67

    Article  PubMed  CAS  Google Scholar 

  • Gampe RT, Montana VG, Lambert MH et al (2000) Asymetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors. Mol Cell 5:545–555

    Article  PubMed  CAS  Google Scholar 

  • Gavrilova O, Haluzik M, Matsusue K et al (2003) Liver PPARγ contributes to hepatic steatosis, triglyceride clearance, and regulation of body fat mass. J Biol Chem 278:34268–34276

    Article  PubMed  CAS  Google Scholar 

  • Ge H, Guermah M, Yuan CX et al (2002) Thr TRAP220 subunit of the TRAP/ mediator is required for PPARγ2-stimulated adipogenesis. Nature 417:563–567

    Article  PubMed  CAS  Google Scholar 

  • Gelman L, Zhou G, Fajas L et al (1999) p300 interacts with the N- and C-terminal part of PPARγ2 in a ligand-independent and -dependent manner, respectively. J Biol Chem 274:7681–7688

    Article  PubMed  CAS  Google Scholar 

  • Girnun GD, Smith WM, Drori S et al (2002) APC-dependent suppression of colon carcinogenesis by PPARγ. Proc Natl Acad Sci 99:13771–13776

    Article  PubMed  CAS  Google Scholar 

  • Grau R, Iñiguez MA, Fresno M (2004) Inhibition of activator protein 1 activation, vascular endothelial growth factor, and cyclooxygenase-2 expression by 15-Deoxy-Δ12,14-Prostaglandin J2 in colon carcinoma cells: evidence for a redox-sensitive Peroxisome Proliferator-activated receptor-γ-independent mechanism. Cancer Res 64:5162–5171

    Article  PubMed  CAS  Google Scholar 

  • Guan rj RJ, Ford HL, Fu Y et al (2000) Drg-1 as a differentiation-related, putative metastatic suppressor gene in human colon cancer. Cancer Res 60:749–755

    PubMed  Google Scholar 

  • Gupta RA, DuBois RN (2001) Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer 1:11–21

    Article  PubMed  CAS  Google Scholar 

  • Gupta RA, Dubois RN (2002) Controversy: PPARγ as a target for treatment of colorectal cancer. Am J Physiol Gastrointest Liver Physiol 283:G266-G269

    PubMed  CAS  Google Scholar 

  • Gupta RA, Brockman JA, Sarraf P et al (2001) Target genes of peroxisome proliferator-activated receptor γ in colorectal cancer cells. J Biol Chem 276:29681–29687

    Article  PubMed  CAS  Google Scholar 

  • Gupta RA, Sarraf P, Brockman JA et al (2003a) Peroxisome proliferator-activated receptor γ and transforming growth factor-β pathways inhibit intestinal epithelial cell growth by regulating levels of TSC-22. J Biol Chem 278:7431–7438

    Article  PubMed  CAS  Google Scholar 

  • Gupta RA, Sarraf P, Mueller E et al (2003b) Peroxisome Proliferator-activated receptor γ-mediated differentiation. J Biol Chem 278:22669–22677

    Article  PubMed  CAS  Google Scholar 

  • Han S, Sidell N, Fisher PB et al (2004) Up-regulation of p21 gene expression by Peroxisome Proliferator-activated receptor γ in human lung carcinoma cells. Clin Cancer Res 10:1911–1919

    Article  PubMed  CAS  Google Scholar 

  • Hauser S, Adelmant G, Sarraf P et al (2000) Degradation of the peroxisome proliferator-activated receptor γ is linked to ligand-dependent activation. J Biol Chem 275:18527–18533

    Article  PubMed  CAS  Google Scholar 

  • Havener AL, He W, Barak Y et al (2003) Muscle-specific PPARγ deletion causes insulin resistance. Nat Med 9:1491–1497

    Article  CAS  Google Scholar 

  • He W, Barak Y, Havener A et al (2003) Adipose-specific PPARγ knockout causes insulin resistance in fat and liver but not in muscle. Proc Natl Acad Sci USA 99:1491–1497

    Google Scholar 

  • Hiragun A, Sato M, Matsui H (1988) Preadipocyte differentiation in vitro: Identification of a highly active adipogenic agent. J Cell Phys 134:124–130

    Article  CAS  Google Scholar 

  • Hong J, Samudio I, Liu S et al (2004) Peroxisome proliferator-activated receptor γ-dependent activation of p21 in Panc-28 pancreatic cancer cells involves Sp1 and Sp4 proteins. Endocrinol 145:5774–5785

    Article  CAS  Google Scholar 

  • Hsi LC, Wilson L, Nixon J et al (2001) 15-Lipoxygenase-1 metabolites down-regulate peroxisome proliferator-activated receptor γ via the MAPK signalling pathway. J Biol Chem 276:34545–34552

    Article  PubMed  CAS  Google Scholar 

  • Huang JT, Welch JS, Ricote M et al (1999) Interleukin-4 dependent production of PPAR-gamma ligands in macrophages by 12/15 lipoxygenase. Nature 400:378–382

    Article  PubMed  CAS  Google Scholar 

  • Huin C, Corriveau L, Bianchi A et al (2000) Differential expression of peroxisome proliferator-activated receptors (PPARs) in the developing human fetal digestive tract. J Histochem Cytochem 48:603–611

    PubMed  CAS  Google Scholar 

  • Ignatenko NA, Babbar N, Mehta D et al (2004) Suppression of polyamine catabolism by activated Ki-ras in human colon cancer cells. Mol Carcinogenesis 39:91–102

    Article  CAS  Google Scholar 

  • Ikezoe T, Miller CW, Kawano S et al (2001) Mutational analysis of the peroxisome proliferator-activated receptor γ gene in human malignancies. Cancer Res 61:5307–5310

    PubMed  CAS  Google Scholar 

  • John A, Tuszynski G (2001) The role of matrix metalloproteinases in tumor angiogenesis and tumor metastasis. Pathol Oncol Res 7:14–23

    Article  PubMed  CAS  Google Scholar 

  • Kato M, Kusumi T, Tsuchida S et al (2004) Induction of differentiation and peroxisome proliferators-activated receptor γ expression in colon cancer cell lines by troglitazone. J Cancer Res Clin Oncol 130:73–79

    Article  PubMed  CAS  Google Scholar 

  • Kim K, Pang KM, Evans M et al (2000) Overexpression of β-catenin induces apoptosis independent of its transactivation function with LEF-1 or the involvement of major G1 cell cycle regulators. Mol Biol Cell 11:3509–3523

    PubMed  CAS  Google Scholar 

  • Kim EJ, Park KS, Chung SY et al (2003) Peroxisome proliferator-activated receptor-γ activator 15-deoxy-Δ12,14-Prostaglandin J2 inhibits neuroblastoma cell growth through induction of apoptosis: Association with extracellular signal-regulated kinase signal pathway. J Pharmacol Exper Therapeutics 307:505–517

    Article  CAS  Google Scholar 

  • Kitamura S, Miyazaki Y, Shinomura Y et al (1999) Peroxisome proliferator-activated receptor γ induces growth arrest and differentiation markers of human colon cancer cells. Jpn J Cancer Res 90:75–80

    PubMed  CAS  Google Scholar 

  • Kliewer SA, Xu HE, Lambert MH et al (2001) Peroxisome proliferators-activated receptors: From genes to physiology. Rec Prog Hormone Res 56:239–263

    Article  CAS  Google Scholar 

  • Knouff C, Auwerx J (2004) Peroxisome Proliferator-Activated Receptor-γ calls for activation in moderation: lessons from genetics and pharmacology. Endocrine Rev 25:899–918

    Article  CAS  Google Scholar 

  • Kohno H, Yoshitani S, Takashima S et al (2001) Troglitazone, a ligand for peroxisome proliferators-activated receptor γ, inhibits chemically-induced aberrant crypt foci in rats. Jpn J Cancer Res 92:396–403

    PubMed  CAS  Google Scholar 

  • Konstantinopoulos PA, Vandoros GP, Sotiropoulou-Bonikou G, et al (2006) NF-κB/PPARγ and/or AP-1/PPARγ ‘on/off’ switches and induction of CBP in colon adenocarcinomas : correlation with COX-2 expression. Int J Colorectal Dis DOI 10.1007/s00384–006–0112-y

  • Koutnikova H, Cock TA, Watanabe M et al (2003) Compensation by the muscle limits the metabolic consequences of lipodystrophy in PPARγ hypomorphic mice. Proc Natl Acad Sci USA 100:14457–14462

    Article  PubMed  CAS  Google Scholar 

  • Lefebvre A-M, Chen I, Desreumaux P et al (1998) Activation of the peroxisome proliferator-activated receptor γ promotes the development of colon tumors in C57BL/6J-APCMin/+ mice. Nat Med 4:1053–1057

    Article  PubMed  CAS  Google Scholar 

  • Lefebvre A-M, Paulweber B, Fajas L et al (1999) Peroxisome proliferator-activated receptor gamma is induced during differentiation of colon epithelium cells. J Endocrinol 162:331–340

    Article  PubMed  CAS  Google Scholar 

  • Lehmann JM, Lenhard JM, Oliver BB et al (1997) Peroxisome proliferator-activated receptors α and γ are activated by indomethacin and other non-steroidal anti-inflammatory drugs. J Biol Chem 272:3406–3410

    Article  PubMed  CAS  Google Scholar 

  • Linsalata M, Giannini R, Notarnicola M, Cavallini A (2006) Peroxisome-proliferator-activated receptor gamma and spermidine/spermine N’-acetyltransferase gene expressions are significantly correlated in human colorectal cancer. BMC Cancer 6:191

    Article  PubMed  CAS  Google Scholar 

  • Mansén A, Guardiola-Diaz H, Rafter J et al (1996) Expression of the Peroxisome Proliferator-Activated Receptor (PPAR) in the mouse colonic mucosa. Biochem Biophys Res Commun 222:844–851

    Article  PubMed  Google Scholar 

  • Matsusue K, Haluzik M, Lambert G et al (2003) Liver-specific disruption of PPARγ in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes. J Clin Invest 111:737–747

    PubMed  CAS  Google Scholar 

  • Ming M, Yu J-P, Meng X-Z et al (2006) Effect of ligand troglitazone on peroxisome proliferators-activated receptor γ expression and cellular growth in human colon cancer cells. World J Gastroenterol 12:7263–7270

    PubMed  CAS  Google Scholar 

  • Morrison RF, Farmer SR (1999) Role of PPARγ in regulating a cascade expression of cyclin-dependent kinase inhibitors, p18 (INK4c) and p21 (Waf1/Cip1), during adipogenesis. J Biol Chem 274:17088–17097

    Article  PubMed  CAS  Google Scholar 

  • Mukherjee R, Davies PJA, Crombie DL et al (1997) Sensitization of diabetic and obese mice to insulin by retinoid X receptor agonists. Nature 386:407–410

    Article  PubMed  CAS  Google Scholar 

  • Nagy L, Tontonoz P, Alvarez JG et al (1998) Oxidized LDL regulates macrophage gene expression through ligand activation of PPARgamma. Cell 93:229–240

    Article  PubMed  CAS  Google Scholar 

  • Niho N, Takahashi M, Kitamura T et al (2003a) Concomitant suppression of hyperlipidemia and intestinal polyp formation in Apc-deficient mice by Peroxisome Proliferator-activated Receptor ligands. Cancer Res 63:6090–6095

    PubMed  CAS  Google Scholar 

  • Niho N, Takahashi M, Shoji Y et al (2003b) Dose-dependent suppression of hyperlipidemia and intestinal polyp formation in Min mice by pioglitazone, a PPARγ ligand. Cancer Sci 94:960–964

    Article  PubMed  CAS  Google Scholar 

  • Nolte RT, Wisely GB, Westin S et al (1998) Ligand binding and co-activator assembly of the peroxisome proliferators-activated receptor-γ. Nature 395:137–143

    Article  PubMed  CAS  Google Scholar 

  • Norris AW et al (2003) Muscle-specific PPARγ-deficient mice develop increased adiposity and insulin resistance but respond to thiazolidinediones. J Clin Invest 112:608–618

    PubMed  CAS  Google Scholar 

  • Okura T, Nakamura M, Takata Y et al (2000) Troglitazone induces apoptosis via the p53 and Gadd45 pathway in vascular smooth muscle cells. Eur J Pharmacol 407:227–235

    Article  PubMed  CAS  Google Scholar 

  • Oshima M, Dinchuk JE, Kargman SL et al (1996) Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2(Cox-2). Cell 87:803–809

    Article  PubMed  CAS  Google Scholar 

  • Ohshima T, Koga H, Shimotohno K (2004) Transcriptional activity of peroxisome proliferator-activated receptor γ is modulated by SUMO-1 modification. J Biol Chem 279:29551–29557

    Article  PubMed  CAS  Google Scholar 

  • Panigrahy D, Singer S, Shen LQ et al (2002) PPARγ ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis. J Clin Invest 110:923–932

    PubMed  CAS  Google Scholar 

  • Panigrahy D, Huang S, Kieran MW et al (2005) PPARγ as a therapeutic target for tumor angiogenesis and metastasis. Cancer Biol Ther 4:687–693

    Article  PubMed  CAS  Google Scholar 

  • Patel L, Pass I, Coxon P et al (2001) Tumor suppressor and anti-inflammatory actions of PPARγ agonists are mediated via upregulation of PTEN. Curr Biol 11:764–768

    Article  PubMed  CAS  Google Scholar 

  • Pino MV, Kelley MF, Jayyosi Z (2004) Promotion of colon tumors in C57BL/6J-APCMin/+ mice by thiazolidinedione PPARgamma agonists and a structurally unrelated PPARgamma agonist. Toxicol Pathol 32:58–63

    Article  PubMed  CAS  Google Scholar 

  • Powell WS (2003) 15-deoxy-Δ12,14-PGJ2: endogenous PPARγ ligand or minor eicosanoid degradation product? J Clin Invest 112:828–830

    PubMed  CAS  Google Scholar 

  • Puigserver P, Spiegelman BM (2003) Peroxisome proliferators-activated receptor-γ coactivator 1α (PGC-1α): Transcriptional coactivator and metabolic regulator. Endocrine Rev 24:78–90

    Article  CAS  Google Scholar 

  • Qin C, Burghardt R, Smith R et al (2003) Peroxisome proliferators-activated receptor γ agonists induce proteasome-dependent degradation of cyclin D1 and estrogen receptor α in MCF-7 breast cancer cells. Cancer Res 63:958–964

    PubMed  CAS  Google Scholar 

  • Ricote M, Huang J, Fajas L et al (1998) Expression of the peroxisome proliferator-activated receptor γ (PPARγ) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein. Proc Natl Acad Sci USA 95:7614–7619

    Article  PubMed  CAS  Google Scholar 

  • Rossi A, Kapahl P, Natoll G et al (2000) Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IκB kinase. Nature 403:103–108

    Article  PubMed  CAS  Google Scholar 

  • Rumi MAK, Ishihara S, Kadowaki Y et al (2004) Peroxisome proliferators-activated receptor γ-dependent and -independent growth inhibition of gastrointestinal tumour cells. Genes Cells 9:1113–1123

    Article  PubMed  CAS  Google Scholar 

  • Sabatino L, Casamassimi A, Peluso G et al (2005) A novel peroxisome proliferator-activated receptor γ isoform with dominant negative activity generated by alternative splicing. J Biol Chem 280:26517–26525

    Article  PubMed  CAS  Google Scholar 

  • Saez E, Tontonoz P, Nelson MC et al (1998) Activators of the nuclear receptor PPARγ enhance colon polyp formation. Nat Med 4:1058–1061

    Article  PubMed  CAS  Google Scholar 

  • Sarraf P, Mueller E, Jones D et al (1998) Differentiation and reversal of malignant changes in colon cancer through PPARγ. Nat Med 4:1046–1052

    Article  PubMed  CAS  Google Scholar 

  • Sarraf P, Mueller E, Smith WM et al (1999) Loss-of-function mutations in PPARγ associated with human colon cancer. Mol Cell 3:799–804

    Article  PubMed  CAS  Google Scholar 

  • Sasaki T, Yoshida K, Shimura H et al (2006) Inhibitory effect of linoleic acid on transformation of IEC6 intestinal cells by in vitro azoxymethane treatment. Int J Cancer 118:593–599

    Article  PubMed  CAS  Google Scholar 

  • Schild RL, Schaiff WT, Carlson MG et al (2002) The activity of PPARγ in primary human trophoblasts is enhanced by oxidized lipids. J Clin Endocrinol Metab 87:1105–1110

    Article  PubMed  CAS  Google Scholar 

  • Schopfer FJ, Lin Y, Baker PRS et al (2005) Nitrolinoleic acid: an endogenous peroxisome proliferator-activated receptor γ ligand. Proc Natl Acad Sci USA 102:2340–2345

    Article  PubMed  CAS  Google Scholar 

  • Seiler N, Raul F (2005) Polyamines and apoptosis. J Cell Mol Med 9:623–642

    Article  PubMed  CAS  Google Scholar 

  • Shao J, Sheng H, DuBois RN (2002) Peroxisome Proliferator-activated receptors modulate K-Ras-mediated transformation of intestinal epithelial cells. Cancer Res 62:3282–3288

    PubMed  CAS  Google Scholar 

  • Sharma C, Pradeep A, Wong L et al (2004) Peroxisome proliferators-activated receptor γ activation can regulate β-catenin levels via a proteasome-mediated and adenomatous polyposis coli-independent pathway. J Biol Chem 279:35583–35594

    Article  PubMed  CAS  Google Scholar 

  • Shimada T, Kojima K, Yoshiura K et al (2002) Characteristics of the peroxisome proliferator activated receptor γ (PPARγ) ligand induced apoptosis in colon cancer cells. Gut 50:658–664

    Article  PubMed  CAS  Google Scholar 

  • Straus DS, Pascual G, Li M et al (2000) 15-Deoxy-Δ12,14-prostaglandin J2 inhibits multiple steps in the NF-κB signaling pathway. Proc Natl Acad Sci 97:4844–4849

    Article  PubMed  CAS  Google Scholar 

  • Subbaramaiah K, Lin DT, Hart JC et al (2001) Peroxisome Proliferator-activated receptor γ ligands suppress the transcriptional activation of cyclooxygenase-2. J Biol Chem 276:12440–12448æ

    Article  PubMed  CAS  Google Scholar 

  • Sugimura A, Kiriyama Y, Nochi H et al (1999) Troglitazone suppresses cell growth of myeloid leukaemia cell lines by induction of p21WAF1/CIP1 cyclin-dependent kinase inhibitor. Biochem Biophys Res Commun 261:833–837

    Article  PubMed  CAS  Google Scholar 

  • Suh N, Wang Y, Honda T et al (1999) A novel synthetic triterpenoid, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, with potent differentiating, antiproliferative, and anti-inflammatory activity. Cancer Res 59:336–341

    PubMed  CAS  Google Scholar 

  • Sundvold H, Lien S (2001) Identification of a novel peroxisome proliferators-activated receptor (PPAR) γ promoter in man and transactivation by the nuclear receptor RORα1. Biochem Biophys Res Commun 287:383–390

    Article  PubMed  CAS  Google Scholar 

  • Takeda K, Ichiki T, Tokunou T et al (2001) 15-Deoxy-Δ12,14-prostaglandin J2 and thiazolidinediones activate the MEK/ERK pathway through phosphatidylinositol 3-kinase in vascular smooth muscle cells. J Biol Chem 276:48950–48955

    Article  PubMed  CAS  Google Scholar 

  • Takashima T, Fujiwara Y, Higuchi K et al (2001) PPAR-gamma ligands inhibit growth of human esophageal adenocarcinoma cells through induction of apoptosis, cell cycle arrest and reduction of ornithine decarboxylase activity. Int J Oncol 19:465–471

    PubMed  CAS  Google Scholar 

  • Tanaka T, Kohno H, Yoshitani S et al (2001) Ligands for Peroxisome Proliferator-activated Receptors α and γ inhibit chemically induced colitis and formation of aberrant crypt foci in rats. Cancer Res 61:2424–2428

    PubMed  CAS  Google Scholar 

  • Tontonoz P, Singer S, Forman BM et al (1997) Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferators-activated receptor γ and the retinoid X receptor. Proc Natl Acad Sci 94:237–241

    Article  PubMed  CAS  Google Scholar 

  • Tsujie M, Nakamori S, Okami J et al (2003) Thiazolidinediones inhibit growth of gastrointestinal, biliary, and pancreatic adenocarcinoma cells through activation of the peroxisome proliferators-activated receptor γ/ retinoid X receptor α pathway. Experimental Cell Res 289:143–151

    Article  CAS  Google Scholar 

  • Vigouroux C, Fajas L, Khallouf E et al (1998) Human peroxisome proliferator-activated receptor-γ2 Genetic mapping, identification of a variant in the coding sequence, and exclusion as the gene responsible for lipoatrophic diabetes. Diabetes 47:490–492

    Article  PubMed  CAS  Google Scholar 

  • Wang M, Wise SC, Leff T et al (1999) Troglitazone, an antidiabetic agent, inhibits cholesterol biosynthesis through a mechanism independent of peroxisome proliferator-activated receptor-γ. Diabetes 48:254–260

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Porter WW, Suh N et al (2000) A synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), is a ligand for the peroxisome proliferator-activated receptor γ. Mol Endocrinol 14:1550–1556

    Article  PubMed  CAS  Google Scholar 

  • Wang C, Fu M, D’Amico M et al (2001) Inhibition of cellular proliferators through Iκkinase-independent and peroxisome proliferator-activated receptor γ-dependent repression of cyclin D1. Mol Cell Biol 21:3057–3070

    Article  PubMed  CAS  Google Scholar 

  • Wang C, Pattabiraman N, Zhou JN et al (2003) Cyclin D1 repression of Peroxisome Proliferator-activated receptor γ expression and transactivation. Mol Cell Biol 23:6159–6173

    Article  PubMed  CAS  Google Scholar 

  • Yang W-L, Frucht H (2001) Activation of the PPAR pathway induces apoptosis and COX-2 inhibition in HT-29 human colon cancer cells. Carcinogenesis 22:1379–1383

    Article  PubMed  CAS  Google Scholar 

  • Yang K, Fan K-H, Lamprecht SA et al (2005) Peroxisome proliferator-activated receptor γ agonist troglitazone induces colon tumors in normal C57BL/6J mice and enhances colonic carcinogenesis in Apc1638+/− Mlh1+/− double mutant mice. Int J Cancer 116:495–499

    Article  PubMed  CAS  Google Scholar 

  • Yki-Järvinen H (2004) Thiazolidinediones. N Engl J Med 351:1106–1118

    Article  PubMed  Google Scholar 

  • Yu Y, Correll PH, Vanden Heuvel JP (2002) Conjugated linoleic acid decreases production of pro-inflammatory products in macrophages: evidence for a PPARγ-dependent mechanism. Biochim Biophys Acta 1581:89–99

    PubMed  CAS  Google Scholar 

  • Zhang B, Berger J, Zhou G et al (1996) Insulin and mitogen-activated protein kinase-mediated phosphorylation and activation of peroxisome proliferators-activated receptor γ. J Biol Chem 271:31771–31774

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Medical Oncology, University Hospital of Larissa, Larissa, 41110, Greece

    Ioannis A. Voutsadakis

Authors
  1. Ioannis A. Voutsadakis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ioannis A. Voutsadakis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Voutsadakis, I.A. Peroxisome proliferator-activated receptor γ (PPARγ) and colorectal carcinogenesis. J Cancer Res Clin Oncol 133, 917–928 (2007). https://doi.org/10.1007/s00432-007-0277-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-007-0277-y

Keywords

Search

Navigation