A novel mechanism of PPARγ regulation of TGFβ 1: Implication in cancer biology

PPAR Research

Volumn , Issue , 2008, Pages

  Lee, Chang Ho ^a   Kim, Hyung Don ^b   Shin, Sang Mi ^c   Kim, Sang Geon ^c  

^a Hanyang University   (South Korea)

^b Chung Ang University   (South Korea)

^c Seoul National University   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; CIGLITAZONE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; RAPAMYCIN; RETINOID X RECEPTOR; TRANSFORMING GROWTH FACTOR BETA1; TROGLITAZONE;

CARCINOGENESIS; CELL DIFFERENTIATION; CELL GROWTH; CELL SURVIVAL; CYTOLOGY; DRUG ACTIVITY; DRUG MECHANISM; ENZYME INHIBITION; ENZYME REGULATION; FIBROSIS; HUMAN; METASTASIS; NONHUMAN; PROTEIN PHOSPHORYLATION; REVIEW; SIGNAL TRANSDUCTION; TUMOR GROWTH;

EID: 47349119166     PISSN: 16874757     EISSN: 16874765     Source Type: Journal    
DOI: 10.1155/2008/762398     Document Type: Review

References (115)

1. Rahimi R. A., Leof E. B., TGF- β signaling: a tale of two responses Journal of Cellular Biochemistry 2007 102 3 593 608
2. Piek E., Heldin C.-H., Dijke P. T., Specificity, diversity, and regulation in TGF- β superfamily signaling The FASEB Journal 1999 13 15 2105 2124
3. Roberts A. B., Sporn M. B., Differential expression of the TGF- β isoforms in embryogenesis suggests specific roles in developing and adult tissues Molecular Reproduction and Development 1992 32 2 91 98
4. Jarrar M. H., Baranova A., PPAR γ activation by thiazolidinediones (TZDs) may modulate breast carcinoma outcome: the importance of interplay with TGF β signalling Journal of Cellular and Molecular Medicine 2007 11 1 71 87
5. Fu M., Zhang J., Zhu X., Peroxisome proliferator-activated receptor γ inhibits transforming growth factor β -induced connective tissue growth factor expression in human aortic smooth muscle cells by interfering with Smad3 Journal of Biological Chemistry 2001 276 49 45888 45894
6. Wang W., Liu F., Chen N., Peroxisome proliferator-activated receptor- γ (PPAR- γ) agonists attenuate the profibrotic response induced by TGF- β 1 in renal interstitial fibroblasts Mediators of Inflammation 2007 2007 7
7. Zhao C., Chen W., Yang L., Chen L., Stimpson S. A., Diehl A. M., PPAR γ agonists prevent TGF β 1/Smad3-signaling in human hepatic stellate cells Biochemical and Biophysical Research Communications 2006 350 2 385 391
8. Li Y., Wen X., Spataro B. C., Hu K., Dai C., Liu Y., Hepatocyte growth factor is a downstream effector that mediates the antifibrotic action of peroxisome proliferator-activated receptor- γ agonists Journal of the American Society of Nephrology 2006 17 1 54 65
9. Zhou S., Lechpammer S., Greenberger J. S., Glowacki J., Hypoxia inhibition of adipocytogenesis in human bone marrow stromal cells requires transforming growth factor- β /Smad3 signaling Journal of Biological Chemistry 2005 280 24 22688 22696
10. Liang X., Kanjanabuch T., Mao S.-L., Plasminogen activator inhibitor-1 modulates adipocyte differentiation American Journal of Physiology 2006 290 1 E103 E113
11. Redondo S., Ruiz E., Santos-Gallego C. G., Padilla E., Tejerina T., Pioglitazone induces vascular smooth muscle cell apoptosis through a peroxisome proliferator-activated receptor- γ, transforming growth factor- β 1, and a Smad2-dependent mechanism Diabetes 2005 54 3 811 817
12. Guo B., Koya D., Isono M., Sugimoto T., Kashiwagi A., Haneda M., Peroxisome proliferator-activated receptor- γ ligands inhibit TGF- β 1-induced fibronectin expression in glomerular mesangial cells Diabetes 2004 53 1 200 208
13. Han J., Hajjar D. P., Tauras J. M., Feng J., Gotto A. M. Jr., Nicholson A. C., Transforming growth factor- β 1 (TGF- β 1) and TGF- β 2 decrease expression of CD36, the type B scavenger receptor, through mitogen-activated protein kinase phosphorylation of peroxisome proliferator-activated receptor- γ Journal of Biological Chemistry 2000 275 2 1241 1246
14. Ahdjoudj S., Kaabeche K., Holy X., Transforming growth factor- β inhibits CCAAT/enhancer-binding protein expression and PPAR γ activity in unloaded bone marrow stromal cells Experimental Cell Research 2005 303 1 138 147
15. Zheng S., Chen A., Disruption of transforming growth factor- β signaling by curcumin induces gene expression of peroxisome proliferator- activated receptor- γ in rat hepatic stellate cells American Journal of Physiology 2007 292 1 G113 G123
16. Kim S.-J., Glick A., Sporn M. B., Roberts A. B., Characterization of the promoter region of the human transforming growth factor- β 1 gene Journal of Biological Chemistry 1989 264 1 402 408
17. Öklü R., Hesketh R., The latent transforming growth factor β binding protein (LTBP) family Biochemical Journal 2000 352, part 3 601 610
18. Lee S. J., Yang E. K., Kim S. G., Peroxisome proliferator-activated receptor- γ and retinoic acid X receptor α represses the TGF β 1 gene via PTEN-mediated p70 ribosomal S6 kinase-1 inhibition: role for Zf9 dephosphorylation Molecular Pharmacology 2006 70 1 415 425
19. Weigert C., Brodbeck K., Bierhaus A., Häring H. U., Schleicher E. D., c-Fos-driven transcriptional activation of transforming growth factor β -1: inhibition of high glucose-induced promoter activity by thiazolidinediones Biochemical and Biophysical Research Communications 2003 304 2 301 307
20. Inagaki Y., Nemoto T., Nakao A., Interaction between GC Box binding factors and Smad proteins modulates cell lineage-specific α 2(I) collagen gene transcription Journal of Biological Chemistry 2001 276 19 16573 16579
21. Inagaki Y., Mamura M., Kanamaru Y., Constitutive phosphorylation and nuclear localization of Smad3 are correlated with increased collagen gene transcription in activated hepatic stellate cells Journal of Cellular Physiology 2001 187 1 117 123
22. Massagué J., Chen Y.-G., Controlling TGF- β signaling Genes and Development 2000 14 6 627 644
23. Piek E., Ju W. J., Heyer J., Functional characterization of transforming growth factor β signaling in Smad2- and Smad3-deficient fibroblasts Journal of Biological Chemistry 2001 276 23 19945 19953
24. Wrana J. L., Regulation of Smad activity Cell 2000 100 2 189 192
25. Vindevoghel L., Lechleider R. J., Kon A., SMAD3/4-dependent transcriptional activation of the human type VII collagen gene (COL7A1) promoter by transforming growth factor β Proceedings of the National Academy of Sciences of the United States of America 1998 95 25 14769 14774
26. Feng X.-H., Lin X., Derynck R., Smad2, Smad3 and Smad4 cooperate with Sp1 to induce p 15 I n k 4 B transcription in response to TGF- β The EMBO Journal 2000 19 19 5178 5193
27. Dennler S., Itoh S., Vivien D., ten Dijke P., Huet S., Gauthier J.-M., Direct binding of Smad3 and Smad4 to critical TGF β -inducible elements in the promoter of human plasminogen activator inhibitor-type 1 gene The EMBO Journal 1998 17 11 3091 3100
28. Frey R. S., Mulder K. M., Involvement of extracellular signal-regulated kinase 2 and stress-activated protein kinase/Jun N -terminal kinase activation by transforming growth factor β in the negative growth control of breast cancer cells Cancer Research 1997 57 4 628 633
29. Watanabe H., de Caestecker M. P., Yamada Y., Transcriptional cross-talk between Smad, ERK1/2, and p38 mitogen-activated protein kinase pathways regulates transforming growth factor- β -induced aggrecan gene expression in chondrogenic ATDC5 cells Journal of Biological Chemistry 2001 276 17 14466 14473
30. Hayashida T., Decaestecker M., Schnaper H. W., Cross-talk between ERK MAP kinase and Smad signaling pathways enhances TGF-beta-dependent responses in human mesangial cells The FASEB Journal 2003 17 11 1576 1578
31. Furukawa F., Matsuzaki K., Mori S., p38 MAPK mediates fibrogenic signal through Smad3 phosphorylation in rat myofibroblasts Hepatology 2003 38 4 879 889
32. Uemura M., Swenson E. S., Gaça M. D. A., Giordano F. J., Reiss M., Wells R. G., Smad2 and Smad3 play different roles in rat hepatic stellate cell function and α -smooth muscle actin organization Molecular Biology of the Cell 2005 16 9 4214 4224
33. Liu X., Wang W., Hu H., Smad3 specific inhibitor, naringenin, decreases the expression of extracellular matrix induced by TGF- β 1 in cultured rat hepatic stellate cells Pharmaceutical Research 2006 23 1 82 89
34. Kang K. W., Kim Y. G., Cho M. K., Oltipraz regenerates cirrhotic liver through CCAAT/enhancer binding protein-mediated stellate cell inactivation The FASEB Journal 2002 16 14 1988 1990
35. Muraoka-Cook R. S., Dumont N., Arteaga C. L., Dual role of transforming growth factor β in mammary tumorigenesis and metastatic progression Clinical Cancer Research 2005 11 2 937s 943s
36. Derynck R., Akhurst R. J., Balmain A., TGF- β signaling in tumor suppression and cancer progression Nature Genetics 2001 29 2 117 129
37. Truty M. J., Urrutia R., Basics of TGF- β and pancreatic cancer Pancreatology 2007 7 5-6 423 435
38. Hannon G. J., Beach D., p 15 I N K 4 B is a potential effector of TGF- β -induced cell cycle arrest Nature 1994 371 6494 257 261
39. Datto M. B., Li Y., Panus J. F., Howe D. J., Xiong Y., Wang X.-F., Transforming growth factor β induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism Proceedings of the National Academy of Sciences of the United States of America 1995 92 12 5545 5549
40. Pietenpol J. A., Holt J. T., Stein R. W., Moses H. L., Transforming growth factor β 1 suppression of c-myc gene transcription: role in inhibition of keratinocyte proliferation Proceedings of the National Academy of Sciences of the United States of America 1990 87 10 3758 3762
41. Alexandrow M. G., Kawabata M., Aakre M., Moses H. L., Overexpression of the c-myc oncoprotein blocks the growth-inhibitory response but is required for the mitogenic effects of transforming growth factor β 1 Proceedings of the National Academy of Sciences of the United States of America 1995 92 8 3239 3243
42. Kang Y., Chen C.-R., Massagué J., A self-enabling TGF β response coupled to stress signaling: Smad engages stress response factor ATF3 for Id1 repression in epithelial cells Molecular Cell 2003 11 4 915 926
43. Siegel P. M., Massagué J., Cytostatic and apoptotic actions of TGF- β in homeostasis and cancer Nature Reviews Cancer 2003 3 11 807 820
44. Kim S. G., Jong H.-S., Kim T.-Y., Transforming growth factor- β 1 induces apoptosis through Fas ligand-independent activation of the Fas death pathway in human gastric SNU-620 carcinoma cells Molecular Biology of the Cell 2004 15 2 420 434
45. Chipuk J. E., Bhat M., Hsing A. Y., Ma J., Danielpour D., Bcl-xL blocks transforming growth factor- β 1-induced apoptosis by inhibiting cytochrome c release and not by directly antagonizing Apaf-1-dependent caspase activation in prostate epithelial cells Journal of Biological Chemistry 2001 276 28 26614 26621
46. Arias A. M., Epithelial mesenchymal interactions in cancer and development Cell 2001 105 4 425 431
47. Thiery J. P., Epithelial-mesenchymal transitions in tumour progression Nature Reviews Cancer 2002 2 6 442 454
48. Hugo H., Ackland M. L., Blick T., Epithelial-mesenchymal and mesenchymal-epithelial transitions in carcinoma progression Journal of Cellular Physiology 2007 213 2 374 383
49. Gal A., Sjöblom T., Fedorova L., Imreh S., Beug H., Moustakas A., Sustained TGF β exposure suppresses Smad and non-Smad signalling in mammary epithelial cells, leading to EMT and inhibition of growth arrest and apoptosis Oncogene 2008 27 9 1218 1230
50. Pardali K., Moustakas A., Actions of TGF- β as tumor suppressor and pro-metastatic factor in human cancer Biochimica et Biophysica Acta 2007 1775 1 21 62
51. Medici D., Hay E. D., Goodenough D. A., Cooperation between snail and LEF-1 transcription factors is essential for TGF- β 1-induced epithelial-mesenchymal transition Molecular Biology of the Cell 2006 17 4 1871 1879
52. Van Aelst L., Symons M., Role of Rho family GTPases in epithelial morphogenesis Genes and Development 2002 16 9 1032 1054
53. Friese M. A., Wischhusen J., Wick W., RNA interference targeting transforming growth factor- β enhances NKG2D-mediated antiglioma immune response, inhibits glioma cell migration and invasiveness, and abrogates tumorigenicity in vivo Cancer Research 2004 64 20 7596 7603
54. Coras R., Hölsken A., Seufert S., The peroxisome proliferator-activated receptor- γ agonist troglitazone inhibits transforming growth factor- β -mediated glioma cell migration and brain invasion Molecular Cancer Therapeutics 2007 6 6 1745 1754
55. Leivonen S.-K., Ala-aho R., Koli K., Grénman R., Peltonen J., Kähäri V.-M., Activation of Smad signaling enhances collagenase-3 (MMP-13) expression and invasion of head and neck squamous carcinoma cells Oncogene 2006 25 18 2588 2600
56. Leivonen S.-K., Kähäri V.-M., Transforming growth factor- β signaling in cancer invasion and metastasis International Journal of Cancer 2007 121 10 2119 2124
57. Deckers M., van Dinther M., Buijs J., The tumor suppressor Smad4 is required for transforming growth factor β -induced epithelial to mesenchymal transition and bone metastasis of breast cancer cells Cancer Research 2006 66 4 2202 2209
58. Kang Y., He W., Tulley S., Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway Proceedings of the National Academy of Sciences of the United States of America 2005 102 39 13909 13914
59. Wick W., Platten M., Weller M., Glioma cell invasion: regulation of metalloproteinase activity by TGF- β Journal of Neuro-Oncology 2001 53 2 177 185
60. Rooprai H. K., Rucklidge G. J., Panou C., Pilkington G. J., The effects of exogenous growth factors on matrix metalloproteinase secretion by human brain tumour cells British Journal of Cancer 2000 82 1 52 55
61. Johansson N., Ala-aho R., Uitto V., Expression of collagenase-3 (MMP-13) and collagenase-1 (MMP-1) by transformed keratinocytes is dependent on the activity of p38 mitogen-activated protein kinase Journal of Cell Science 2000 113 2 227 235
62. Lin S.-W., Lee M.-T., Ke F.-C., TGF β 1 stimulates the secretion of matrix metalloproteinase 2 (MMP2) and the invasive behavior in human ovarian cancer cells, which is suppressed by MMP inhibitor BB3103 Clinical & Experimental Metastasis 2000 18 6 493 499
63. Giehl K., Imamichi Y., Menke A., Smad4-independent TGF- β signaling in tumor cell migration Cells Tissues Organs 2007 185 1-3 123 130
64. Li M. O., Wan Y. Y., Sanjabi S., Robertson A.-K. L., Flavell R. A., Transforming growth factor- β regulation of immune responses Annual Review of Immunology 2006 24 99 146
65. Kehrl J. H., Wakefield L. M., Roberts A. B., Production of transforming growth factor β by human T lymphocytes and its potential role in the regulation of T cell growth Journal of Experimental Medicine 1986 163 5 1037 1050
66. Ma A., Koka R., Burkett P., Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis Annual Review of Immunology 2006 24 657 679
67. Wrzesinski S. H., Wan Y. Y., Flavell R. A., Transforming growth factor- β and the immune response: implications for anticancer therapy Clinical Cancer Research 2007 13 18 5262 5270
68. Ahmadzadeh M., Rosenberg S. A., TGF- β 1 attenuates the acquisition and expression of effector function by tumor antigen-specific human memory CD8 T cells Journal of Immunology 2005 174 9 5215 5223
69. Rook A. H., Kehrl J. H., Wakefield L. M., Effects of transforming growth factor β on the functions of natural killer cells: depressed cytolytic activity and blunting of interferon responsiveness Journal of Immunology 1986 136 10 3916 3920
70. Bellone G., Aste-Amezaga M., Trinchieri G., Rodeck U., Regulation of NK cell functions by TGF- β 1 Journal of Immunology 1995 155 3 1066 1073
71. Geissmann F., Revy P., Regnault A., TGF- β 1 prevents the noncognate maturation of human dendritic Langerhans cells Journal of Immunology 1999 162 8 4567 4575
72. Grommes C., Landreth G. E., Heneka M. T., Antineoplastic effects of peroxisome proliferator-activated receptor γ agonists Lancet Oncology 2004 5 7 419 429
73. Girnun G. D., Smith W. M., Drori S., APC-dependent suppression of colon carcinogenesis by PPAR γ Proceedings of the National Academy of Sciences of the United States of America 2002 99 21 13771 13776
74. Ikezoe T., Miller C. W., Kawano S., Mutational analysis of the peroxisome proliferator-activated receptor γ in human malignancies Cancer Research 2001 61 13 5307 5310
75. Sarraf P., Mueller E., Smith W. M., Loss-of-function mutations in PPAR γ associated with human colon cancer Molecular Cell 1999 3 6 799 804
76. Kubota T., Koshizuka K., Williamson E. A., Ligand for peroxisome proliferator-activated receptor γ (troglitazone) has potent antitumor effect against human prostate cancer both in vitro and in vivo Cancer Research 1998 58 15 3344 3352
77. Chen G. G., Lee J. F., Wang S. H., Chan U. P. F., Ip P. C., Lau W. Y., Apoptosis induced by activation of peroxisome-proliferator activated receptor-gamma is associated with Bcl-2 and Nf- κ B in human colon cancer Life Sciences 2002 70 22 2631 2646
78. Brockman J. A., Gupta R. A., Dubois R. N., Activation of PPAR γ leads to inhibition of anchorage-independent growth of human colorectal cancer cells Gastroenterology 1998 115 5 1049 1055
79. Kato M., Kusumi T., Tsuchida S., Tanaka M., Sasaki M., Kudo H., Induction of differentiation and peroxisome proliferator-activated receptor γ expression in colon cancer cell lines by troglitazone Journal of Cancer Research and Clinical Oncology 2004 130 2 73 79
80. Ohta K., Endo T., Haraguchi K., Hershman J. M., Onaya T., Ligands for peroxisome proliferator-activated receptor γ inhibit growth and induce apoptosis of human papillary thyroid carcinoma cells Journal of Clinical Endocrinology and Metabolism 2001 86 5 2170 2177
81. Sarraf P., Mueller E., Jones D., Differentiation and reversal of malignant changes in colon cancer through PPAR γ Nature Medicine 1998 4 9 1046 1052
82. Yu J., Qiao L., Zimmermann L., Troglitazone inhibits tumor growth in hepatocellular carcinoma in vitro and in vivo Hepatology 2006 43 1 134 143
83. Heaney A. P., Fernando M., Melmed S., PPAR- γ receptor ligands: novel therapy for pituitary adenomas Journal of Clinical Investigation 2003 111 9 1381 1388
84. Day C., Thiazolidinediones: a new class of antidiabetic drugs Diabetic Medicine 1999 16 3 179 192
85. Weng J.-R., Chen C.-Y., Pinzone J. J., Ringel M. D., Chen C.-S., Beyond peroxisome proliferator-activated receptor γ signaling: the multi-facets of the antitumor effect of thiazolidinediones Endocrine-Related Cancer 2006 13 2 401 413
86. Palakurthi S. S., Aktas H., Grubissich L. M., Mortensen R. M., Halperin J. A., Anticancer effects of thiazolidinediones are independent of peroxisome proliferator-activated receptor γ and mediated by inhibition of translation initiation Cancer Research 2001 61 16 6213 6218
87. Bae M.-A., Song B. J., Critical role of c-Jun N-terminal protein kinase activation in troglitazone-induced apoptosis of human HepG2 hepatoma cells Molecular Pharmacology 2003 63 2 401 408
88. Baek S. J., Wilson L. C., Hsi L. C., Eling T. E., Troglitazone, a peroxisome proliferator-activated receptor γ (PPAR γ) ligand, selectively induces the early growth response-1 gene independently of PPAR γ: a novel mechanism for its anti-tumorigenic activity Journal of Biological Chemistry 2003 278 8 5845 5853
89. Sugimura A., Kiriyama Y., Nochi H., Troglitazone suppresses cell growth of myeloid leukemia cell lines by induction of p21WAF1/CIP1 cyclin-dependent kinase inhibitor Biochemical and Biophysical Research Communications 1999 261 3 833 837
90. Lefebvre A.-M., Chen I., Desreumaux P., Activation of the peroxisome proliferator-activated receptor γ promotes the development of colon tumors in C57BL/6J- APC M i n / + mice Nature Medicine 1998 4 9 1053 1057
91. Saez E., Rosenfeld J., Livolsi A., PPAR γ signaling exacerbates mammary gland tumor development Genes and Development 2004 18 5 528 540
92. Park E. Y., Cho I. J., Kim S. G., Transactivation of the PPAR-responsive enhancer module in chemopreventive glutathione S -transferase gene by the peroxisome proliferator-activated receptor- γ and retinoid X receptor heterodimer Cancer Research 2004 64 10 3701 3713
93. Chou F.-S., Wang P.-S., Kulp S., Pinzone J. J., Effects of thiazolidinediones on differentiation, proliferation, and apoptosis Molecular Cancer Research 2007 5 6 523 530
94. Thompson E. A., PPAR γ physiology and pathology in gastrointestinal epithelial cells Molecules and Cells 2007 24 2 167 176
95. Kodera Y., Takeyama K., Murayama A., Suzawa M., Masuhiro Y., Kato S., Ligand type-specific interactions of peroxisome proliferator-activated receptor γ with transcriptional coactivators Journal of Biological Chemistry 2000 275 43 33201 33204
96. Kang K. W., Cho I. J., Lee C. H., Kim S. G., Essential role of phosphatidylinositol 3-kinase-dependent CCAAT/enhancer binding protein β activation in the induction of glutathione S -transferase by oltipraz Journal of the National Cancer Institute 2003 95 1 53 66
97. Kang K. W., Park E. Y., Kim S. G., Activation of CCAAT/enhancer-binding protein β by 2 ′ -amino- 3 ′ -methoxyflavone (PD98059) leads to the induction of glutathione S -transferase A2 Carcinogenesis 2003 24 3 475 482
98. Holmbeck S. M. A., Dyson H. J., Wright P. E., DNA-induced conformational changes are the basis for cooperative dimerization by the DNA binding domain of the retinoid X receptor Journal of Molecular Biology 1998 284 3 533 539
99. Jenö P., Ballou L. M., Novak-Hofer I., Thomas G., Identification and characterization of a mitogen-activated S6 kinase Proceedings of the National Academy of Sciences of the United States of America 1988 85 2 406 410
100. de Groot R. P., Ballou L. M., Sassone-Corsi P., Positive regulation of the cAMP-responsive activator CREM by the p70 S6 kinase: an alternative route to mitogen-induced gene expression Cell 1994 79 1 81 91
101. Harada H., Andersen J. S., Mann M., Terada N., Korsmeyer S. J., p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD Proceedings of the National Academy of Sciences of the United States of America 2001 98 17 9666 9670
102. Wang X., Li W., Williams M., Terada N., Alessi D. R., Proud C. G., Regulation of elongation factor 2 kinase by p 90 R S K 1 and p70 S6 kinase The EMBO Journal 2001 20 16 4370 4379
103. Zhu J., Wu J., Frizell E., Rapamycin inhibits hepatic stellate cell proliferation in vitro and limits fibrogenesis in an in vivo model of liver fibrosis Gastroenterology 1999 117 5 1198 1204
104. Biecker E., De Gottardi A., Neef M., Long-term treatment of bile duct-ligated rats with rapamycin (sirolimus) significantly attenuates liver fibrosis: analysis of the underlying mechanisms Journal of Pharmacology and Experimental Therapeutics 2005 313 3 952 961
105. Sabatini D. M., Erdjument-Bromage H., Lui M., Tempst P., Snyder S. H., RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs Cell 1994 78 1 35 43
106. Lee K. S., Park S. J., Hwang P. H., PPAR-gamma modulates allergic inflammation through up-regulation of PTEN The FASEB Journal 2005 19 8 1033 1035
107. Liu J.-L., Sheng X., Hortobagyi Z. K., Mao Z., Gallick G. E., Yung W. K. A., Nuclear PTEN-mediated growth suppression is independent of Akt down-regulation Molecular and Cellular Biology 2005 25 14 6211 6224
108. Weigert C., Brodbeck K., Bierhaus A., Häring H. U., Schleicher E. D., c-Fos-driven transcriptional activation of transforming growth factor β -1: inhibition of high glucose-induced promoter activity by thiazolidinediones Biochemical and Biophysical Research Communications 2003 304 2 301 307
109. Salbert G., Fanjul A., Piedrafita F. J., Retinoic acid receptors and retinoid X receptor- α down-regulate the transforming growth factor- β 1 promoter by antagonizing AP-1 activity Molecular Endocrinology 1993 7 10 1347 1356
110. Narla G., Heath K. E., Reeves H. L., KLF6, a candidate tumor suppressor gene mutated in prostate cancer Science 2001 294 5551 2563 2566
111. Slavin D. A., Koritschoner N. P., Prieto C. C., López-Díaz F. J., Chatton B., Bocco J. L., A new role for the Krüppel-like transcription factor KLF6 as an inhibitor of c-Jun proto-oncoprotein function Oncogene 2004 23 50 8196 8205
112. Ratziu V., Lalazar A., Wong L., Zf9, a Kruppel-like transcription factor up-regulated in vivo during early hepatic fibrosis Proceedings of the National Academy of Sciences of the United States of America 1998 95 16 9500 9505
113. Kim Y., Ratziu V., Choi S.-G., Transcriptional activation of transforming growth factor β 1 and its receptors by the Kruppel-like factor Zf9/core promoter-binding protein and Sp1: potential mechanisms for autocrine fibrogenesis in response to injury Journal of Biological Chemistry 1998 273 50 33750 33758
114. Warke V. G., Nambiar M. P., Krishnan S., Transcriptional activation of the human inducible nitric-oxide synthase promoter by Krüppel-like factor 6 Journal of Biological Chemistry 2003 278 17 14812 14819
115. Patel L., Pass I., Coxon P., Downes C. P., Smith S. A., Macphee C. H., Tumor suppressor and anti-inflammatory actions of PPAR γ agonists are mediated via upregulation of PTEN Current Biology 2001 11 10 764 768