Peroxisome proliferator-activated receptor-γ ligands for the treatment of breast cancer

Expert Opinion on Investigational Drugs

Volumn 14, Issue 6, 2005, Pages 557-568

  Fenner, Martin H ^a   Elstner, Elena ^b  

^a HUMBOLDT UNIVERSITY   (Germany)

^b NONE

Author keywords

Apoptosis; Breast cancer; Differentiation; Nuclear hormone receptor; PPAR ; Proliferation; Thiazolidinedione

Indexed keywords

15 DEOXY DELTA12,14 PROSTAGLANDIN J2; 2 [1 CARBOXY 2 [4 [2 (5 METHYL 2 PHENYL 4 OXAZOLYL)ETHOXY]PHENYL]ETHYLAMINO]BENZOIC ACID METHYL ESTER; 2 [2 PROPYL 3 [3 [2 ETHYL 4 (4 FLUOROPHENYL) 5 HYDROXYPHENOXY]PROPOXY]PHENOXY]BENZOIC ACID; 2,4 THIAZOLIDINEDIONE DERIVATIVE; 4 [2 (5,6,7,8 TETRAHYDRO 5,5,8,8 TETRAMETHYL 2 NAPHTHYL) 1,3 DIOXOLAN 2 YL]BENZOIC ACID; [2 METHYL 4 [4 METHYL 2 (4 TRIFLUOROMETHYLPHENYL) 5 THIAZOLYLMETHYLTHIO]PHENOXY]ACETIC ACID; ANTINEOPLASTIC AGENT; AROMATASE INHIBITOR; BEXAROTENE; BEZAFIBRATE; CIGLITAZONE; CS 7017; ETODOLAC; FIBRIC ACID DERIVATIVE; GLUCOSE; GW 0072; HORMONE RECEPTOR STIMULATING AGENT; INDOLE DERIVATIVE; INDOMETACIN; IRBESARTAN; ISOTRETINOIN; L 746604; LG 10068; LIPID; MURAGLITAZAR; NETOGLITAZONE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PIOGLITAZONE; RAGAGLITAZAR; RETINOIC ACID; RETINOID X RECEPTOR; ROSIGLITAZONE; SDX 101; SPIROLAXINE; TAMOXIFEN; TELMISARTAN; TESAGLITAZAR; TRASTUZUMAB; TRITERPENOID; TROGLITAZONE; TZD 18; UNCLASSIFIED DRUG;

APOPTOSIS; BODY WEIGHT DISORDER; BREAST CANCER; BREAST TUMOR; CANCER CELL CULTURE; CANCER INHIBITION; CANCER INVASION; CANCER PATIENT; CLINICAL TRIAL; DRUG MECHANISM; DRUG POTENTIATION; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; EXPERIMENTAL NEOPLASM; FLUID RETENTION; GLUCOSE METABOLISM; HUMAN; IN VITRO STUDY; IN VIVO STUDY; LIPID METABOLISM; LIVER TOXICITY; METABOLIC REGULATION; METASTASIS; MITOSIS INHIBITION; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS CANCER; REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION; TRANSCRIPTION INITIATION; TRANSCRIPTION REGULATION; TREATMENT FAILURE; TUMOR VASCULARIZATION; WEIGHT GAIN;

ANIMALS; ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; CLINICAL TRIALS; HUMANS; LIGANDS; PPAR GAMMA; SIGNAL TRANSDUCTION;

EID: 21244432740     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.14.6.557     Document Type: Review

References (128)

1. KERSTEN S, DESVERGNE B, WAHLI W. Roles of PPARs in health and disease. Nature (2000) 405:421-424.
2. KOEFFLER HP: Peroxisome proliferator-activated receptor-γ and cancers. Clin. Cancer Res. (2003) 9:1-9.
3. PANIGRAHY D, SHEN LQ, KIERAN MW, KAIPAINEN A. Therapeutic potential of thiazolidinediones as anticancer agents. Erpert Opin. Investig. Drugs (2003) 12:1925-1937.
4. THEOCHARISA S, MARGELI A, KOURAKILIS G: Peroxisome proliferator activated receptor-γ ligands as potent antineoplastic agents. Curr. Med. Chem. AntiCanc. Agents (2003) 3:239-251.
5. GROMMES C, LANDRETH GE, HENEKA MT. Antineoplastic effects of peroxisome, proliferator-activated receptor-γ agonists. Lancet Oncol. (2004) 5:419-429.
6. MICHALIK L, DESVERGNE B, WAHLI W: Peroxisome-proliferator-activated receptors and cancers: complex stories. Nat. Rev. Cancer (2004) 4:61-70.
7. RUMI MA, ISHIHARA S, KAZUMORI H, KADOWAKI Y, KINOSHITA Y: Can PPAR-γ ligands be used in cancer therapy? Curr. Med. Chem. AntiCanc. Agents (2004) 4:465-77.
8. HAYS T, RUSYN I, BURNS AM et al.: Role of peroyisome proliferator-activated receptor-α (PPAR-α) in bezafibrate-induced hepatocarcinogenesis and cholestasis. Carcinogenesis (2005) 26:219-227.
9. ISSEMANN I, GREEN S: Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature (1990) 347:645-650.
10. TUGWOOD JD, ISSEMANN I, ANDERSON RG, BUNDELL KR, McPHEAT WL, GREEN S: The mouse peroxisome proliferator activated receptor recognizes a response element in die 5′ flanking sequence of the rat acyl CoA oxidase gene. EMBO J. (1992) 11:433-9.
11. ISSEMANN I, PRINCE RA, TUGWOOD JD, GREEN S: The peroxisome proliferator-activated receptor: retinoid X receptor heterodimer is activated by fatty acids and fibratc hypolipidaemic drugs. J. Mol. Endocrinol. (1993) 11:37-47.
12. STAELS B, DALLONGEVILLE J, AUWERX J, SCHOONJANS K, LEITERSDORF E, FRUCHART JC: Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation (1998) 98:2088-93.
13. SCHMIDT A, ENDO N, RUTLEDGE SJ, VOGEL R, SHINAR D, RODAN GA: Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids. Mol. Endocrinol. (1992) 6:1634-1641.
14. MICHALIK L, DERVERGNE B, TAN NS et al.: Impaired skin wound healing in peroxisome proliferator-activated receptor (PPAR)-α and PPAR-β mutant mice. J. Cell Biol. (2001) 154:799-814.
15. HE TC, CHAN TA, VOGELSTEIN B, KINZLER KW. PPAR-δ is an APC-regulated target of nonsteroidal anti-inflammatory drugs. Cell (1999) 99:335-345.
16. PARK BH, VOGELSTEIN B, KINZLER KW. Genetic disruption of PPARδ decreases the tumorigenicity of human colon cancer cells. Proc. Natl. Acad. Sci. USA (2001) 98:2598-2603.
17. HARMAN FS, NICOL CJ, MARIN HE, WARD JM, GONZALEZ FJ, PETERS JM: Peroxisome proliferator-activated receptor-δ attenuates colon carcinogenesis. Nat. Med. (2004) 10:481-483.
18. TONTONOZ P, HU E, SPIEGELMAN BM: Stimulation of adipogenesis in fibroblasts by PPAR-γ2, a lipid-activated transcription factor. Cell (1994) 79:1147-1156.
19. LEHMANN JM, MOORE LB, SMITH-OLIVER TA, WILKINSON WO, WILLSON TM, KLIEWER SA: An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor-γ (PPAR-γ). J. Biol. Chem. (1995) 270:12953-12956.
20. CHANG AY, WYSE BM, GILCHRIST BJ, PETERSON T, DIANI AR: Ciglitazone, a new hypoglycemic agent. I. Studies in ob/ob and db/db mice, diabetic Chinese hamsters, and normal and streprozotocin-diabetic rats. Diabetes (1983) 32:830-838.
21. FAJAS L, AUBOEF D, RASPE E et al.: The organization, promoter analysis, and expression of the human PPAR-γ gene. J. Biol. Chem. (1997) 272:18779-18789.
22. HU E, TONOTONOZ P, SPIEGELMAN BM: Transdifferentiation of myoblasts by the adipogenic transcription factors PPAR-γ and C /EBP-α. Proc. Natl. Acad. Sci. USA (1995) 92:9856-9860.
23. 2 metabolite binds peroxisome proliferator-activated receptor-γ and promotes adipocyte differentiation. Cell (1995) 83:813-819.
24. FORMAN BM, TONOTNOZ P, CHEN J, BRUN RP, SPIEGELMAN BM, EVANS RM: 15-Deoxy-δ12,14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR-γ. Cell (1995) 83:803-812.
25. BERGER J, LEIBOWITCZ MD, DOEBBER TW et al.: Novel peroxisome proliferator-activated receptor (PPAR)-γ and PPAR-δ ligands produce distinct biological effects. J. Biol. Chem. (1999) 274:6718-6725.
26. PLACE AE, SUH N, WILLIAMS CR et al.: The novel synthetic triterpenoid, CDDO-imidazolide, inhibits inflammatory response and tumour growth in vivo. Clin. Cancer Res. (2003) 9:2798-2806.
27. QIN C, MORROW D, STEWART J et al.: A new class of peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists that inhibit growth of breast cancer cells: 1,1-Bis(3′-indolyl)-1-(p-substituted phenyl)methanes. Mol. Cancer Ther. (2004) 3:247-260.
28. 4 receptor antagonist LY-293111 inhibits proliferation and induces apoptosis in human pancreatic cancer cells. Clin. Cancer Res. (2002) 8:3232-3242.
29. COPLAND JA, KURAKATA S, FUJIWARA K et al.: A novel high affinity PPAR-γ agonist inhibits human anaplastic thyroid tumour growth. AACR Annual Meeting, Orlando, USA (2004):LB-17.
30. KOLLURI SK, CORR M, JAMES SY et al.: The (R)-enantiomer of the nonsteroidal anti-inflammatory drug etodolac binds retinoid X receptor and induces tumour-selective apoptosis. Proc. Natl. Acad. Sci. USA (2005) 102:2525-2530.
31. RIVAL Y, STENNEVIN A, PUECH L et al.: Human adipocyte fatty acid-binding protein (aP2) gene promoter-driven reporter assay discriminates nonlipogenic peroxisome proliferator-activated receptor-γ ligands. J. Pharmacol. Exp. Ther. (2004) 311:467-75.
32. REGINATO MJ, BAILEY ST, KRAKOW SL et al.: A potent antidiabetic thiazolidinedione with unique peroxisome proliferator-activated receptor-γ-activating properties. J. Biol. Chem. (1998) 273:32679-84.
33. ELBRECHT A, CHEN Y, ADAMS A et al.: L-764406 is a partial agonist of human peroxisome proliferator-activated receptor-γ. The role of Cys313 in ligand binding. J. Biol. Chem. (1999) 274:7913-7922.
34. OBERFIELD JL, COLLINS JL, HOLMES CP et al.: A peroxisome proliferator-activated receptor-γ ligand inhibits adipocyte differentiation. Proc. Natl. Acad. Sci. USA (1999) 96:6102-6106.
35. DOGGRELL SA: Telmisartan - killing two birds with one stone. Expert Opin. Pharmacother. (2004) 5:2397-2400.
36. SCHUPP M, GINESTE R, CLEMENZ M et al.: PPAR-γ activating angiotensin receptor blockers exhibit differential cofactor recruitment and induce a divergent gene expression profile in 3T3-L1 adipocytes. 3rd International Symposium on PPARS. Monte Carlo, Monaco (19 - 23 March 2005):11.
37. LJUNG B, BAMBERG K, DAHLLOF B et al.: AZ-242, a novel PPAR-α/γ agonist with beneficial effects on insulin resistance and carbohydrate and lipid metabolism in ob/ob mice and obese Zucker rats. J. Lipid Res. (2002) 43:1855-1863.
38. GUO Q, SAHOO SP, WANG PR et al.: A novel peroxisome proliferator-activated receptor-α/γ dual agonist demonstrates favorable effects on lipid homeostasis. Endocrinology (2004) 145:1640-1648.
39. DEVASTRALE PV, CHEN S, JEON Y et al.: Design and synthesis of N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5-methyl -2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine [Muraglitazar/BMS-298585], a novel peroxisome proliferator-activated receptor-α/γ dual agonist with efficacious glucose and lipid-lowering activities. J. Med. Chem (2005) 48:2248-2250.
40. PICKAVANCE LC, BRAND CL, WASSERMANN K, WILDING JP: The dual PPAR-α/γ agonist, ragaglitazar, improves insulin sensitivity and metabolic profile equally with pioglirazone in diabetic and dietary obese ZDF rats. Br. J. Pharmacol. (2005) 144:308-316.
41. LIU DC, ZANG CB, LIU HY, POSSINGER. K, FAN SG, ELSTNER E: A novel PPAR-α/γ dual agonist inhibits cell growth and induces apoptosis in human glioblastoma. T98G cells. Acta Pharmacol. Sin. (2004) 25:1312-1319.
42. WESTIN S, KUROKAWA R, NOLTE RT et al.: Interactions controlling the assembly of nuclear-receptor heterodimers and co-activators. Nature (1998) 395:199-202.
43. MIZUKAMI J, TANIGUCHI T: The antidiabetic agent thiazolidinedione stimulates the interaction between PPAR-γ and CBP. Biochem. Biophys. Res. Commun. (1997) 240:61-64.
44. NOLTE RT, WISELY GB, WESTIN S et al.: Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-γ. Nature (1998) 395:137-143.
45. BERGER JP: PPAR ligands and mechanisms: an update. 3rd International Symposium on PPARS. Monte Carlo, Monaco (19 - 23 March 2005):2.
46. TEMPLE KA, COHEN RN, WONDISFORD SR, YU C, DEPLEWSKI D, WONDISFORD FE: An intact DNA-binding domain is not required for peroxisome pfoliferator-activated receptor-γ (PPAR-γ) binding and activation on some PPAR response elements. J. Biol. Chem. (2005) 280:3529-3540.
47. GE K, GUERMAH M, YUAN CX et al.: Transcription co-activator TRAP220 is required for PPAR-γ2-stimulated adipogenesis. Nature (2002) 417:563-567.
48. WALLBERG AE, YAMAMURA S, MALIK S, SPEIGELMAN BM, ROEDER RG: Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through co-activator PGC-1α. Mol. Cell (2003) 12:1137-1149.
49. PUIGSERVER P, ADELMANT G, WU Z et al.: Activation of PPAR-γ co-activator-1 through transcription factor docking. Science (1999) 286:1368-1371.
50. MUELLER E, DRORI S, AIYER A et al.: Genetic analysis of adipogenesis through peroxisome proliferator-activated receptor-γ isoforms. J. Biol. Chem. (2002) 277:41925-41930.
51. SHI Y, HON M, EVANS RM: The peroxisome proliferator-activated receptor-δ, an integrator of transcriptional repression and nuclear receptor signalling. Proc. Natl. Acad. Sci. USA (2002) 99:2613-2618.
52. YU C, MARKAN K, TEMPLE KA, DEPLEWSKI D, BRADY MJ, COHEN RN: The nuclear receptor corepressors NCoR and SMRT decrease PPAR-γ transcriptional activity and repress 3T3-L1 adipogenesis. J. Biol. Chem. (2005) 280:13600-13605.
53. PICARD F, KURTEV M, CHUNG N et al.: Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ. Nature (2004) 429:771-776.
54. FLOYD ZE, STEPHENS JM: Control of peroxisome proliferator-activated receptor-γ2 stability and activity by SUMOylation. Obes. Res. (2004) 12:921-928.
55. OHSHIMA T, KOGA H, SHIMOTOHNO K: Transcriptional activity of peroxisome proliferator-activated receptor-γ is modulated by SUMO-1 modification. J. Biol. Chem. (2004) 279:29551-29557.
56. SUCHANEK KM, MAY FJ, ROBINSON JA et al.: Peroxisome proliferator-activated receptor-α in the human breast cancer cell lines MCF-7 and MDA-MB-231. Mol. Carcinog. (2002) 34:165-171.
57. SUCHANEK KM, MAY FJ, LEE WJ, HOLMAN NA, ROBERTS-THOMSON SJ: Peroxisome proliferator-activated receptor β expression in human breast epithelial cell lines of tumorigenic and non-tumorigenic origin. Int. J. Biochem. Cell Biol. (2002) 34:1051-1058.
58. STEPHEN RL, GUSTAFSSON MC, JARVIS M et al.: Activation of peroxisome proliferator-activated receptor-δ stimulates the proliferation of human breast and prostate cancer cell lines. Cancer Res. (2004) 64:3162-3170.
59. CHAWLA A, BARAK Y, NAGY L, LIAO D, TONOTONOZ P, EVANS RM: PPAR-γ dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation. Nat. Med. (2001) 7:48-52.
60. ROSSI A, KAPAHI P, NATOLI G et al.: Anti-inflammatory cyclopentenone Prostaglandins are direct inhibitors of I-κB kinase. Nature (2000) 403:103-8.
61. STRAUS DS, PASCUAL G, LI M et al.: 15-deoxy-δ 12,14-prostaglandin J2 inhibits multiple steps in the NF-κB signalling pathway. Proc. Natl. Acad. Sci. USA (2000) 97:4844-4849.
62. PALAKURTHI SS, AKTAS H, GRUBISICCHI LM, MORTENSEN RM, HALPERIN JA: Anticancer effects of thiazolidinediones are independent of peroxisome proliferator-activated receptor-γ and mediated by inhibition of translation initiation. Cancer Res. (2001) 61:6213-6218.
63. 2-induced apoptos is does not require PPARγ in breast cancer cells. J. Lipid Res. (2002) 43:1818-1828.
64. TURTURRO F, FRIDAY E, FOWLER R, SURIE D, WELBOURNE T: Troglitazone acts on cellular pH and DNA synthesis through a peroxisome proliferator-activated receptor-γ-independent mechanism in breast cancer-derived cell lines. Clin. Cancer Res. (2004) 10:7022-7030.
65. LEA MA, SURA M, DESBORDES C: Inhibition of cell proliferation by potential peroxisome proliferator-activated receptor (PPAR)-γ agonists and antagonists. AntiCancer Res. (2004) 24:2765-2771.
66. SEARGENT JM, YATES EA, GILL JH: GW-9662, a potent antagonist of PPAR-γ, inhibits growth of breast tumour cells and promotes the anticancer effects of the PPAR-γ agonist rosiglitazone, independently of PPARγ activation. Br. J. Pharmacol. (2004) 143:933-937.
67. SHIAU CW, YANG CC, KULP SK et al.: Thiazolidenediones mediate apoptosis in prostate cancer cells in part through inhibition of Bd-xL/Bcl-2 functions independently of PPAR-γ. Cancer Res. (2005) 65:1561-1569.
68. HUANG JW, SHIAU CW, YANG YT KF et al.: Peroxisome pfoliferator-activated receptor {γ}-independent ablation of cyclin D1 by thiazolidenediones and their derivatives in breast cancer cells. Mol. Pharmacol. (2005) 67:1342-1348.
69. BRAISSANT O, FOUFELLE F, SCOTTO C, DAUCA M, WAHLI W: Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-α, -β, and -γ in the adult rat. Endocrinology (1996) 137:354-366.
70. JAIN S, PULIKURI S, ZHU Y et al.: Differential expression of the peroxisome proliferator-activated receptor-γ (PPAR-γ) and its co-activators steroid receptor co-activator-1 and PPAR-binding protein PBP in the brown fat, urinary bladder, colon, and breast of the mouse. Am. J. Pathol. (1998) 153:349-354.
71. KILGORE MW, TATE PL, RAI S, SENGOKU E, PRICE TM: MCF-7 and T47D human breast cancer cells contain a functional peroxisomal response. Mol. Cell. Endocrinol. (1997) 129:229-235.
72. ELSTNER E, WILLIAMSON EA, ZANG C et al.: Novel therapeutic approach: ligands for PPAR-γ and retinoid receptors induce apoptosis in bcl-2-positive human breast cancer cells. Breast Cancer Res. Treat (2002) 74:155-65.
73. ELSTNER E, MUELLER C, KOSHIZUKA K et al.: Ligands for peroxisome proliferator-activated receptor-γ and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proc. Natl. Acad. Sci. USA (1998) 95:8806-8811.
74. YANG Z, BAGHERI-YARMAND R, BALASENTHIL S et al.: HER2 regulation of peroxisome proliferator-activated receptor-γ (PPAR-γ) expression and sensitivity of breast cancer cells to PPAR-γ ligand therapy. Clin. Cancer Res. (2003) 9:3198-3203.
75. JIANG WG, DOUGLAS-JONES A, MANSEL RE: Expression of peroxisome-proliferator activated receptor-γ (PPAR-γ) and the PPAR-γ co-activator, PGC-1, in human breast cancer correlates with clinical outcomes. Int. J. Cancer (2003) 106:752-757.
76. 2 and 15-deoxy-δ12,14-prostaglandin J2 in human breast cancer and metastasis. Int. J. Cancer (2003) 103:84-90.
77. YEE LD, GUO Y, BRADBURY J, SUSTER S, CLINTON SK, SEEWALDT VL: The antiproliferative effects of PPAR-γ ligands in normal human mammary epithelial cells. Breast Cancer Res. Treat (2003) 78:179-192.
78. IKEZOE T, MILLER CW, KAWANO S et al.: Mutational analysis of the peroxisome proliferator-activated receptor-γ gene in human malignancies. Cancer Res. (2001) 61:5307-5310.
79. KROLL TG, SERRAF P, PECCIARINI L et al.: PAX8-PPARγ1 fusion oncogene in human thyroid carcinoma. Science (2000) 289:1357-1360.
80. POSCH MG, ZANG C, MUELLER W, LASS U, VON DEIMLING A, ELSTNER E: Somatic mutations in peroxisome proliferator-activated receptor-γ are rare events in human cancer cells. Med. Sci. Monit. (2004) 10:BR250-BR254.
81. MEMISOGLU A, HANKINSON SE, MANSON JE, COLDITZ GA, HUNTER DJ: Lack of association of the codon 12 polymorphism of the peroxisome proliferator-activated receptor-γ gene with breast cancer and body mass. Pharmacogenetics (2002) 12:597-603.
82. TONTONOZ P, SINGER S, FORMAN BM et al.: Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor-γ and the retinoid X receptor. Proc. Natl. Acad. Sci. USA (1997) 94:237-241.
83. MUELLER E, SARRAF P, TONTONOZ P et al.: Terminal differentiation of human breast cancer through PPAR-γ. Mol. Cell (1998) 1:465-470.
84. CLAY CE, NAMEN AM, ATSUMI G et al.: Influence of J series prostaglandins on apoptosis and tumourigenesis of breast cancer cells. Carcinogenesis (1999) 20:1905-1911.
85. THEOCHARIS S, MARGELI A, VIELH P, KOUR'AKLIS G: Peroxisome proliferator-activated receptor-γ ligands as cell-cyde modulators. Cancer Treat. Rev. (2004) 30:545-554.
86. WANG C, FU M, D'AMICO M et al.: Inhibition of cellular proliferation through IκB kinase-independent and peroxisome proliferator-activated receptor-γ-dependent repression of cyclin D1. Mol. Cell. Biol. (2001) 21:3057-3070.
87. YIN F, WAKINO S, LIU Z et al.: Troglitazone inhibits growth of MCF-7 breast carcinoma cells by targeting G1 cell cycle regulators. Biochem. Biophys. Res. Commun. (2001) 286:916-922.
88. WANG C, PATTABIRAMAN N, ZHOU JN et al.: Cyclin D1 repression of peroxisome proliferator-activated receptor-γ expression and transactivation. Mol. Cell. Biol. (2003) 23:6159-6173.
89. FU M, RAO M, BOURAS T et al.: Cyclin D1 inhibits peroxisomc proliferator-activated receptor-{γ}-mediated adipogenesis through histone deacetylase recruitment. J. Biol. Chem. (2005) 280:16934-16941.
90. ALTIOK S, XU M, SPIEGLEMAN BM: PPAR-γ induces cell cycle withdrawal: inhibition of E2F/DP DNA-binding activity via downregulation of PP2A. Genes Dev. (1997) 11:1987-1998.
91. KAWA S, NIKAIDO T, UNNO H, USUDA N, NAKAYAMA K, KIYOSAWA K: Growth inhibition and differentiation of pancreatic cancer cell lines by PPAR-γ ligand troglitazone. Pancreas (2002) 24:1-7.
92. MORRISON RF, FARMER SR: Role of PPAR-γ in regulating a cascade expression of cyclin-dependent kinase inhibitors, p18(INK4c) and p21(Waf1/Cip1), during adipogenesis. J. Biol. Chem. (1999) 274:17088-17097.
93. LIU H, ZANG C, FENNER MH, POSSINGER K, ELSTNER E: PPAR-γ ligands and ATRA inhibit the invasion of human breast cancer cells in vitro. Breast Cancer Res. Treat (2003) 79:63-74.
94. LU M, KWAN T, YU C et al.: PPARγ agonists promote TRAIL-induced apoptosis by reducing survivin levels via cyclin D3 repression and cell cycle arrest. J. Biol. Chem. (2005) 280:6742-6751.
95. YIN F, BRUEMMER D, BLASCHKE F, HSUEH WA, LAW RE, HERLE AJ: Signalling pathways involved in induction of GADD45 gene expression and apoptosis by troglitazone in human MCF-7 breast carcinoma cells. Oncogene (2004) 23:4614-4623.
96. MARGELI A, OURAKLIS G, THEOCHARIS S: peroxisome proliferator activated receptor-γ (PPAR-γ) ligands and angiogenesis. Angiogenesis (2003) 6:165-169.
97. INOUE K, KAWAHITO Y, SANO H, TAKANO H, YOSHIKAWA T: New diagnostic tool for tumour angiogenesis. Chest (2003) 123:966-967.
98. XIN X, YANG S, KOWALSKI J, GERRITSEN ME: Peroxisome proliferator-activated receptor-γ ligands are potent inhibitors of angiogenesis in vitro and in vivo. J. Mol. Chem. (1999) 274:9116-9121.
99. GOETZE S, BUNGENSTOCK A, CZUPALLA C et al.: Leptin induces endothelial cell migration through Akt, which is inhibited by PPAR-γ-ligands. Hypertension (2002) 40:748-754.
100. PANIGRAHY D, SINGERS, SHEN LQ et al.: PPAR-γ ligands inhibit primary tumour growth and metastasis by inhibiting angiogenesis. J. Clin. Invest. (2002) 110:923-932.
101. HUANG H, CAMPBELL SC, BEDFORD DF et al.: Peroxisome proliferator-activated receptor-γ ligands improve the antitumour efficacy of thrombospondin peptide ABT510. Mol. Cancer Res. (2004) 2:541-550.
102. IJPENBURG A, TAN NS, GELMAN L et al.: In vivo activation of PPAR target genes by RXR homodimers. EMBO J. (2004) 23:2083-2091.
103. WU K, ZHANG Y, XU XC et al.: The retinoid X receptor-selective retinoid, LGD-1069, prevents the development of oestfogen receptor-negative mammary tumours in transgenic mice. Cancer Res. (2002) 62:6376-6380.
104. ESTEVA FJ, GLASPY J, BAIDAS S et al.: Multicenter Phase II study of oral bexarotene for patients with metastatic breast cancer. J. Clin. Oncol. (2003) 21:999-1006.
105. CROWE DL, CHANDARARATNA RA: A retinoid X receptor (RXR)-selective retinoid reveals that RXR-α is potentially a therapeutic target in breast cancer cell lines, and that it potentiates antiproliferative and apoprotic responses to peroxisome prolifefator-activated receptor ligands. Breast Cancer Res. (2004) 6:R546-R555.
106. JAMES SY, LIN F, KOLLURI SK, DAWSON MI, ZHANG XK: Regulation of retinoic acid receptor β expression by peroxisome proliferator-activated receptor-γ ligands in cancer cells. Cancer Res. (2003) 63:3531-3538.
107. RUBIN GL, ZHAO Y, KALUS AM, SIMPSON ER: Peroxisome proliferator-activated receptor-γ ligands inhibit oestrogen biosynthesis in human breast adipose tissue: possible implications for breast cancer therapy. Cancer Res. (2000) 60:1604-1608.
108. AANDREWS WJ, WINNETT G, REHMAN F, SHANMUGASUNDARAM P, HAGEN D, SCHREY MP: Aromatase inhibition by 15-deoxy-prostaglandin J(2) (15-dPGJ(2)) and N-(4-hydroxyphenyl)-retinamide (4HPR) is associated with enhanced ceramide production. J. Steroid Biochem. Mol. Biol. (2005) 94:159-165.
109. QIN C, BURGHARDT R, SMITH R, WORMKE M, STEWART J, SAFE S: Peroxisome proliferator-activated receptor-γ agonists induce proteasome-dependent degradation of cyclin D1 and oestrogen receptor-α in MCF-7 breast cancer cells. Cancer Pes. (2003) 63:958-964.
110. ZHU Y, QI C, JAIN S et al.: Amplification and overexpression of peroxisome proliferator-activated receptor binding protein (PBP/PPARBP) gene in breast cancer. Proc. Natl. Acad. Sci. USA (1999) 96:10848-10853.
111. BUZDAR AU, IBRAHIM NK, FRANCIS D et al.: Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J. Clin. Oncol. (2005) (In Press).
112. PIGNATELLI M, CORTES-CANTELI M, LAI C, SANTOS A, PEREZ-CASTILLO A: The peroxisome proliferator-activated receptor-γ is an inhibitor of ErbBs activity in human breast cancer cells. J. Cell Sci. (2001) 114:4117-4126.
113. HEDVAT M, JAIN A, CARSON DA et al.: Inhibition of HER-kinase activation prevents ERK-mediated degradation of PPAR-γ. Cancer Cell (2004) 5:565-74.
114. PIGNATELLI M, COCCA C, SANTOS A, PEREZ-CASTILLO A: Enhancement of BRCA1 gene expression by the peroxisome proliferator-activated receptor-γ in the MCF-7 breast cancer cell line. Oncogene (2003) 22:5446-50.
115. BARAK Y, NELSON MC, ONG ES P et al.: PPAR-γ is required for placental, cardiac, and adipose tissue development. Mol. Cell (1999) 4:585-595.
116. CUI Y, MIYOSHI K, CLAUDIO E et al.: Loss of the peroxisome proliferation-activated receptor-γ (PPAR-γ) does not affect mammary development and propensity for tumour formation but leads to reduced fertility. J. Biol. Chem. (2002) 277:17830-17835.
117. JIA Y, QI C, ZHANG Z, ZHU YT, RAO SM, ZHU YJ: PBP null mutation results in defective mammary gland development. J. Biol. Chem. (2005) 280:10766-10773.
118. SAEZ E, ROSENFELD J, LIVOLSKI A et al.: PPAR γ signalling exacerbates mammary gland tumour development. Genes Dev. (2004) 18:528-540.
119. SUH N, WANG Y, WILLIAMS CR et al.: A new ligand for the peroxisome proliferator-activated receptor-γ (PPAR-γ), GW7845, inhibits rat mammary carcinogenesis. Cancer Res. (1999) 59:5671-5673.
120. MEHTA RG, WLLLAMSON E, PATEL MK, KOEFFLER HP: A ligand of peroxisome proliferator-activated receptor-γ, retinoids, and prevention of preneoplastic mammary lesions. J. Natl. Cancer Inst. (2000) 92:418-423.
121. MARTENS FM, VISSERAN FL, LEMAY J, DE KONING EJ, RABELINK TJ: Metabolic and additional vascular effects of thiazolidinediones. Drugs (2002) 62:1463-1480.
122. KOHLROSER J, MATHAI J, REICHHELD J, BANNER BF, BONKOVSKY HL: Hepatotoxicity due to troglitazone: report of two cases and review of adverse events reported to the United States Food and Drug Administration. Am. J. Gastroenterol. (2000) 95:272-276.
123. DEMETRI GD, FLETCHER CD, MUELLER E et al.: Induction of solid tumour differentiation by the peroxisome proliferator-activated receptor-γ ligand troglitazone in patients with liposarcoma. Proc. Natl. Acad. Sci. USA (1999) 96:3951-3956.
124. DEBROCK G, VANHENTENRIJK V, SCIOT R, DEBIEC-RYCHTER M, OYEN R, VAN OOSTEROM A: A Phase II trial with rosiglitazone in liposarcoma patients. Br. J. Cancer (2003) 89:1409-1412.
125. MUELLER E, SMITH M, SARRAF P et al.: Effects of ligand activation of peroxisome proliferator-activated receptor-γ in human prostate cancer. Proc. Natl. Acad. Sci. USA (2000) 97:10990-10995.
126. SMITH MR, MANOLA J, KAUFMAN DS et al.: Rosiglitazone versus placebo for men with prostate carcinoma and a rising serum prostate-specific antigen level after radical prostatectomy and/or radiation therapy. Cancer (2004) 101:1569-1574.
127. KULKE MH, DEMETRI GD, SHARPLESS NE et al.: A Phase II study of troglitazone, an activator of the PPAR-γ receptor, in patients with chemotherapy-resistant metastatic colorectal cancer. Cancer J. (2002) 8:395-399.
128. BURSTEIN HJ, DEMETRI GD, MUELLER E, SARRAF P, SPIEGELMAN BM, WINER EP: Use of the peroxisome proliferator-activated receptor (PPAR)-γ ligand troglitazone as treatment for refractory breast cancer: a Phase II study. Breast Cancer Res. Treat. (2003) 79:391-397.