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Mechanisms of TGF-β-Induced Apoptosis in Cancer Cells

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Book cover Transforming Growth Factor-β in Cancer Therapy, Volume I

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Apoptosis is a common regulatory process of multicellular organisms. Transforming growth factor beta (TGF-β) has essential roles in a variety of apoptotic pathways including the mitochondrial apoptotic, death receptor, and other intracellular signaling pathways. The TGF-β-mediated apoptotic process involves not only intracellular proapoptotic responses but also anti-apoptotic signals. Resistance to TGF-β regulatory signals is the most indicative characteristic of many cancer cells during tumorigenesis. Therefore, controlling the homeostatic balance of these regulatory signals is critical for the prevention of tumorigenesis. Understanding the mechanisms of TGF-β-induced apoptosis in cancer cells will provide new insight of anticancer therapy.

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References

  1. Vaux DL, Korsmeyer SJ. Cell death in development. Cell 1999;96:245–254.

    CAS  PubMed  Google Scholar 

  2. Fas SC, Fritzsching B, Suri-Payer E, Krammer PH. Death receptor signaling and its function in the immune system. Curr Dir Autoimmun 2006;9:1–17.

    CAS  PubMed  Google Scholar 

  3. Twomey C, McCarthy JV. Pathway of apoptosis and importance in development. J Cell Mol Med 2005;9:345–359.

    CAS  PubMed  Google Scholar 

  4. Bissell DM, Roulot D, George J. Transforming growth factor β and the liver. Hepatology 2001; 34:859–867.

    CAS  PubMed  Google Scholar 

  5. Schuster N, Krieglstein K. Mechanisms of TGF-β-mediated apoptosis. Cell Tissue Res 2002; 307:1–14.

    CAS  PubMed  Google Scholar 

  6. Korsmeyer SJ, Gross A, Harada H, et al. Death and survival signals determine active/inactive conformations of pro-apoptotic BAX, BAD, and BID molecules. Cold Spring Harbor Symp Quant Biol 1999;64:343–350.

    CAS  PubMed  Google Scholar 

  7. Harada HB, Becknell M, Wilm M, et al. Phosphorylation and inactivation of BAD by mitochondria-anchored protein kinase A Mol Cell 1999;3:413–422.

    CAS  Google Scholar 

  8. Oltvai ZN, Korsmeyer S. Checkpoints of dueling dimers foil death wishes. Cell 1994;79:189–192.

    CAS  PubMed  Google Scholar 

  9. Condorelli F, Salomoni P, Cotteret S, et al. Caspase cleavage enhances the apoptotis-inducing effects of BAD. Mol. Cell. Biol. 2001;21:3025–3036.

    CAS  PubMed  Google Scholar 

  10. Kim BC, Mamura M, Choi KS, et al. Transforming growth factor β1 induces apoptosis through cleavage of BAD in a Smad3-dependent mechanism in FaO hepatoma cells. Mol Cell Biol 2002;22:1369–1378.

    CAS  PubMed  Google Scholar 

  11. Herrera B, Alvarez AM, Beltran J, et al. Resistance to TGF-β-induced apoptosis in regenerating hepatocytes. J Cell Physiol 2004;201:385–392.

    CAS  PubMed  Google Scholar 

  12. Robinson MJ, Cobb MH. Mitogen-activated protein kinase pathways. Curr Opin Cell Biol 1997;9:180–186.

    CAS  PubMed  Google Scholar 

  13. Park HJ, Kim BC, Kim SJ, et al. Role of MAP kinases and their cross-talk in TGF-β1-induced apoptosis in FaO rat hepatoma cell line. Hepatology 2002;35:1360–1371.

    CAS  PubMed  Google Scholar 

  14. Kim KY, Kim BC, Xu Z, et al. Mixed Lineage Kinase 3 (MLK3)-activated p38 MAP kinase mediates transforming growth factor-β-induced apoptosis in hepatoma cells. J Biol Chem 2004; 279:29,478–29,484.

    CAS  PubMed  Google Scholar 

  15. Dorow DS, Devereux L, Dietzsch E, et al. Identification of a new family of human epithelial protein kinases containing two leucine/isoleucine-zipper domains. Eur J Biochem 1993;213:701–710.

    CAS  PubMed  Google Scholar 

  16. Ing YL, Leung IW, Heng HH, et al. MLK-3: identification of a widely-expressed protein kinase bearing an SH3 domain and a leucine zipper-basic region domain. Oncogene 1994;9:1745–1750.

    CAS  PubMed  Google Scholar 

  17. Gallo KA, Mark MR, Scadden DT, et al. Identification and characterization of SPRK, a novel src-homology 3 domain-containing proline-rich kinase with serine/threonine kinase activity. J Biol Chem 1994;269:15,092–15,100.

    CAS  PubMed  Google Scholar 

  18. Gallo KA, Johnson GL. Mixed-lineage kinase control of JNK and p38 MAPK pathways. Nat Rev Mol Cell Biol 2002;3:663–672.

    CAS  PubMed  Google Scholar 

  19. Rana A, Gallo K, Godowski P, et al. The mixed lineage kinase SPRK phosphorylates and activates the stress-activated protein kinase activator, SEK-1. J Biol Chem 1996;271:19,025–19,028.

    CAS  PubMed  Google Scholar 

  20. Tibbles LA, Ing YL, Kiefer F, et al. MLK-3 activates the SAPK/JNK and p38/RK pathways via SEK1 and MKK3/6. EMBO J 1996;15:7026–7035.

    CAS  PubMed  Google Scholar 

  21. Teramoto H, Coso OA, Miyata H, et al. Signaling from the small GTP-binding proteins Rac1 and Cdc42 to the c-Jun N-terminal kinase/stress-activated protein kinase pathway. J Biol Chem 1996; 271:27,225–27,228.

    CAS  PubMed  Google Scholar 

  22. Hirai S, Katoh M, Terada M, et al. MST/MLK2, a member of the mixed lineage kinase family, directly phosphorylates and activates SEK1, an activator of c-Jun N-terminal kinase/stress-activated protein kinase. J Biol Chem 1997;272:15,167–15,173.

    CAS  PubMed  Google Scholar 

  23. Wiley SR, Schooley K, Smolak PJ, et al. Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 1995;3:673–682.

    CAS  PubMed  Google Scholar 

  24. Walczak H, Degli-Esposti MA, Johnson RS, et al. TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. EMBO J 1997;16:5386–5397.

    CAS  PubMed  Google Scholar 

  25. Ashkenazi A, Pai RC, Fong S, et al. Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest 1999;104:155–162.

    CAS  PubMed  Google Scholar 

  26. Walczak H, Miller RE, Ariail K, et al. Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat Med 1999;5:157–163.

    CAS  PubMed  Google Scholar 

  27. Herzer K, Ganten TM, Schulze-Bergkamen H, et al. Transforming growth factor beta can mediate apoptosis via the expression of TRAIL in human hepatoma cells. Hepatology 2005;42:183–92.

    CAS  PubMed  Google Scholar 

  28. Cretney E, Takeda K, Yagita H, et al. Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient mice. J Immunol 2002;168:1356–1361.

    CAS  PubMed  Google Scholar 

  29. Lin JK, Chou CK. In vitro apoptosis in the human hepatoma cell line induced by transforming growth factor beta1. Cancer Res 1992;52:385–388.

    CAS  PubMed  Google Scholar 

  30. Oberhammer F, Bursch W, Parzefall W, et al. Effect of transforming growth factor beta on cell death of cultured rat hepatocytes. Cancer Res 1991;51:2478–2485.

    CAS  PubMed  Google Scholar 

  31. Laiho M, DeCaprio JA, Ludlow JW, et al. Growth inhibition by TGF-beta linked to suppression of retinoblastoma protein phosphorylation. Cell 1990;62:175–185.

    CAS  PubMed  Google Scholar 

  32. Geiser AG, Burmester JK, Webbink R, et al. Inhibition of growth by transforming growth factor-following fusion of two non-responsive human carcinoma cell lines. J Biol Chem 1992;267:2588–2593.

    CAS  PubMed  Google Scholar 

  33. Kyprianou N, Isaacs JT. Activation of programmed cell death in the rat ventral prostate after castration. Endocrinology 1988;122:552–562.

    CAS  PubMed  Google Scholar 

  34. Sutkowski DM, Fong CJ, Sensibar JA, et al. Interaction of epidermal growth factor and transforming growth factor-beta in human prostatic epithelial cells in culture. Prostate 1992;21:133–143.

    CAS  PubMed  Google Scholar 

  35. Kyprianou N, Isaacs JT. Expression of transforming growth factor-beta in the rat ventral prostate during castration-induced programmed cell death. Mol Endocrinol 1989;3:1515–1522.

    CAS  PubMed  Google Scholar 

  36. Sgambato A, Doki Y, Schieren I, Weinstein IB. Effects of cyclin E overexpression on cell growth and response to transforming growth factor beta depend on cell context and p27Kip1 expression. Cell Growth Differ 1997;8:393–405.

    CAS  PubMed  Google Scholar 

  37. Kim IY, Ahn HJ, Zelner DJ, et al. Loss of expression of transforming growth factor beta type I and type II receptors correlates with tumor grade in human prostate cancer tissues. Clin Cancer Res. 1996;2:1255–1261.

    CAS  PubMed  Google Scholar 

  38. Williams RH, Stapleton AM, Yang G, et al. Reduced levels of transforming growth factor β receptor type II in human prostate cancer: an immunohistochemical study. Clin Cancer Res 1996;2:635–640

    CAS  PubMed  Google Scholar 

  39. Guo Y, Kyprianou N. Restoration of transforming growth factor-β signaling pathway in human prostate cancer cells suppresses tumorigenicity via induction of caspase-1-mediated apoptosis. Cancer Res 1999;59:1366–1371.

    CAS  PubMed  Google Scholar 

  40. Brodin G, ten Dijke PT, Funa K, et al. Increased Smad expression and activation are associated with apoptotsis in normal and malignant prostate after castration. Cancer Res 1999;59:2731–2738.

    CAS  PubMed  Google Scholar 

  41. Marcelli M, Cunningham GR, Walkup M, et al. Signaling pathway activated during apoptosis of the prostate cancer cell line LNCaP: overexpression of caspase-7 as a new gene therapy strategy for prostate cancer. Cancer Res 1999;59:382–390.

    CAS  PubMed  Google Scholar 

  42. Bowen C, Voeller HJ, Kikly K, Gelmann EP. Synthesis of pro-caspase-3 and-7 during apoptosis in prostate cancer cells. Cell Death Differ 1999;6:394–401.

    CAS  PubMed  Google Scholar 

  43. Zhu B, Kyprianou N. Transforming growth factor β and prostate cancer. Cancer Treat Res. 2005;126:157–173.

    PubMed  Google Scholar 

  44. Bruckheimer EM, Kyprianou N. Apoptosis in prostate carcinogenesis; A growth regulator and a therapeutic target. Cell Tissue Res. 2000;301:153–162.

    CAS  PubMed  Google Scholar 

  45. Bello-DeOcampo D, Tindall DJ. TGF-β/Smad signaling in prostate cancer Current Drug Targets 2003;4:197–207.

    CAS  PubMed  Google Scholar 

  46. Hall PA, Coates PJ, Ansari B, Hopwood D. Regulation of cell number in the mammalian gastrointestinal tract: the importance of apoptosis. J Cell Sci 1994;107:3569–3577.

    CAS  PubMed  Google Scholar 

  47. von Herbay A, Rudi J. Role of apoptosis in gastric epithelial turnover. Microsc Res Tech 2000;48:303–311.

    Google Scholar 

  48. Kim SG, Jong HS, Kim TY, et al. Transforming growth factor-beta1 induces apoptosis through Fas ligand-independent activation of the Fas death pathway in human gastric SNU-620 carcinoma cells. Mol Biol Cell 2004;15:420–434.

    CAS  PubMed  Google Scholar 

  49. Yamamura Y, Hua X, Bergelson S, Lodish HF. Critical role of Smads and AP-1 complex in transforming growth factor-β-dependent apoptosis. J Biol Chem 2000;275:36,295–36,302.

    CAS  PubMed  Google Scholar 

  50. Yanagisawa K, Osada H, Masuda A, et al. Induction of apoptosis by Smad3 and down-regulation of Smad3 expression in response to TGF-β in human normal lung epithelial cells. Oncogene 1998;17:1743–1747.

    CAS  PubMed  Google Scholar 

  51. Dai JL, Bansal RK, Kern SE. G1 cell cycle arrest and apoptosis induction by nuclear Smad4/Dpc 4, phenotypes reversed by a tumorigenic mutation. Proc Natl Acad Sci USA 1999;96:1427–1432.

    CAS  PubMed  Google Scholar 

  52. Park JG, et al. Establishment and characterization of human gastric carcinoma cell lines. Int J Cancer 1997;70:443–449.

    CAS  PubMed  Google Scholar 

  53. Lallemand F, Mazars A, Prunier C, et al. Smad7 inhibits the survival nuclear factor kappaB and potentiates apoptosis in epithelial cells. Oncogene 2001;20:879–884.

    CAS  PubMed  Google Scholar 

  54. Edlund S, Bu S, Schuster N, et al. Transforming growth factor-β1 (TGF-β)-induced apoptosis of prostate cancer cells involves Smad7-dependent activation of p38 by TGF-β-activated kinase 1 and mitogen-activated protein kinase kinase 3. Mol Bio. Cell 2003;14:529–544.

    CAS  Google Scholar 

  55. Ju HR, Jung U, Sonn CH, et al. Aberrant signaling of TGF-β1 by the mutant Smad4 in gastric cancer cells. Cancer Lett 2003;196:197–206.

    CAS  PubMed  Google Scholar 

  56. Kang SH, Bang YJ, Im YH, et al. Transcriptional repression of the transforming growth factor-β type I receptor gene by DNA methylation results in the development of TGF-β resistance in human gastric cancer. Oncogene 1999;18:7280–7286.

    CAS  PubMed  Google Scholar 

  57. Park K, Kim SJ, Bang YJ, et al. Genetic changes in the transforming growth factor beta (TGF-β) type II receptor gene in human gastric cancer cells: correlation with sensitivity to growth inhibition by TGF-β. Proc Natl Acad Sci USA 1994;91:8772–8776.

    CAS  PubMed  Google Scholar 

  58. He W, Li AG, Wang D, et al. Overexpression of Smad7 results in severe pathological alterations in multiple epithelial tissues. EMBO J. 2002;21:2580–2590.

    CAS  PubMed  Google Scholar 

  59. Li QL, Ito K, Sakakura C, et al. Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell 2002;109:113–124.

    CAS  PubMed  Google Scholar 

  60. Inoue K, Ozaki S, Shiga T, et al. Runx3 controls the axonal projection of proprioceptive dorsal root ganglion neurons. Nat Neurosci 2002;5:946–954.

    CAS  PubMed  Google Scholar 

  61. Levanon D, Bettoun D, Harris-Cerruti C, et al. The Runx3 transcription factor regulates development and survival of TrkC dorsal root ganglia neurons. EMBO J 2002;21:3454–3463.

    CAS  PubMed  Google Scholar 

  62. Taniuchi I, Osato M, Egawa T, et al. Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development. Cell 2002;111:621–633.

    CAS  PubMed  Google Scholar 

  63. Woolf E, Xiao C, Fainaru O, et al. Runx3 and Runx1 are required for CD8 T cell development during thymopoiesis. Proc Natl Acad Sci USA 2003;100:7731–7736.

    CAS  PubMed  Google Scholar 

  64. Guo WH, Weng LQ, Ito K, et al. Inhibition of growth of mouse gastric cancer cells by Runx3, a novel tumor suppressor. Oncogene 2002;21:8351–8355.

    CAS  PubMed  Google Scholar 

  65. Kim TY, Lee HJ, Hwang KS, et al. Methylation of RUNX3 in various types of human cancers and premalignant stages of gastric carcinoma. Lab Invest 2004;84:479–484.

    CAS  PubMed  Google Scholar 

  66. Oshimo Y, Oue N, Mitani Y, et al. Frequent loss of RUNX3 expression by promoter hypermethylation in gastric carcinoma. Pathobiology 2004;71:137–143.

    CAS  PubMed  Google Scholar 

  67. Chi XZ, Yang JO, Lee KY, Ito K, RUNX3 suppresses gastric epithelial cell growth by inducing p21 (WAF1/Cip1) expression in cooperation with transforming growth factor β-activated SMAD. Mol Cell Biol 2005;25:8097–8107.

    CAS  PubMed  Google Scholar 

  68. Carmeliet P. Angiogenesis in health and disease. Nat Med 2003;9:653–660.

    CAS  PubMed  Google Scholar 

  69. Chavakis E, Dimmeler S. Regulation of endothelial cell survival and apoptosis during angiogenesis. Arterioscler Thromb Vasc Biol 2002;22:887–893.

    CAS  PubMed  Google Scholar 

  70. Folkman J, D’Amore PA. Blood vessel formation: what is its molecular basis? Cell 1996;87:1153–1155.

    CAS  PubMed  Google Scholar 

  71. Jackson C. Matrix metalloproteinases and angiogenesis. Curr Opin Nephrol Hypertens 2002;11:295–299.

    PubMed  Google Scholar 

  72. Pepper MS. Extracellular proteolysis and angiogenesis. Thromb Haemost 2001;86:346–355.

    CAS  PubMed  Google Scholar 

  73. Risau W. Mechanisms of angiogenesis. Nature 1997;386:671–674.

    CAS  PubMed  Google Scholar 

  74. Fajardo LF, Prionas SD, Kwan HH, et al. Transforming growth factor beta1 induces angiogenesis in vivo with a threshold pattern. Lab Invest 1996;74:600–608.

    CAS  PubMed  Google Scholar 

  75. Hirschi KK, Rohovsky SA, D’Amore PA. PDGF, TGF-β, and heterotypic cell-cell interactions mediate endothelial cell-induced recruitment of 10T1/2 cells and their differentiation to a smooth muscle fate. J Cell Biol 2003;141:805–814.

    Google Scholar 

  76. Koh GY, Kim SJ, Klug MG, et al. Targeted expression of transforming growth factor-β1 in intracardiac grafts promotes vascular endothelial cell DNA synthesis. J Clin Invest 1995;95:114–121.

    CAS  PubMed  Google Scholar 

  77. Madri JA, Bell L, Merwin JR. Modulation of vascular cell behavior by transforming growth factors beta. Mol Reprod Dev 1992;32:121–126.

    CAS  PubMed  Google Scholar 

  78. Vernon RB, Sage EH. A novel, quantitative model for study of endothelial cell migration and sprout formation within three-dimensional collagen matrices. Microvasc Res 1999;57:118–133.

    CAS  PubMed  Google Scholar 

  79. Pollman MJ, Naumovski L, Gibbons GH. Vascular cell apoptosis: cell type-specific modulation by transforming growth factor-β1 in endothelial cells versus smooth muscle cells. Circulation 1999; 99:2019–2026.

    CAS  PubMed  Google Scholar 

  80. Schulick AH, Taylor AJ, Zuo W, et al. Overexpression of transforming growth factor beta1 in arterial endothelium causes hyperplasia, apoptosis, and cartilaginous metaplasia. Proc Natl Acad Sci USA 1998;95:6983–6988.

    CAS  PubMed  Google Scholar 

  81. Lebrin F, Deckers M, Bertolino P, et al. TGF-β receptor function in the endothelium. Cardiovascular Res 2005;65:599–608.

    CAS  Google Scholar 

  82. Solovyan VT, Keski-Oja J. Apoptosis of human endothelial cells is accompanied by proteolytic processing of latent TGF-β binding proteins and activation of TGF-β. Cell Death Differ 2005;12:815–826.

    CAS  PubMed  Google Scholar 

  83. Hodge S, Hodge G, Flower R, et al. Up-regulation of production of TGF-β and IL-4 and down-regulation of IL-6 by apoptotic human bronchial epithelial cells. Immunol Cell Biol 2002;80:537–543.

    CAS  PubMed  Google Scholar 

  84. Chen W, Jin W, Tian H, et al. Requirement for transforming growth factor-1 in controlling T cell apoptosis. J Exp Med 2001;194:439–453.

    CAS  PubMed  Google Scholar 

  85. Leksa V, Godar S, Schiller HB, et al. TGF-β-induced apoptosis in endothelial cells mediated by M6P/IGFII-R and mini-plasminogen. J Cell Sci 2005;118:4577–4586.

    CAS  PubMed  Google Scholar 

  86. Ito Y, Miyazono K. RUNX transcription factors as key targets of TGF-β superfamily signaling. Curr Opin Genet Dev 2003;13:43–47.

    CAS  PubMed  Google Scholar 

  87. Westendorf JJ, Hiebert SW. Mammalian runt-domain proteins and their roles in hematopoiesis, osteogenesis, and leukemia J Cell Biochem 2003;32/33:51–58.

    Google Scholar 

  88. Sun L, Vitolo MI, Qiao M, et al. Regulation of TGF-β-mediated growth inhibition and apoptosis by RUNX2 isoforms in endothelial cells. Oncogene 2004;23:4722–4734.

    CAS  PubMed  Google Scholar 

  89. Finch CE, Laping NJ, Morgan TE, et al. TGF-β1 is an organizer of responses to neurodegeneration. J Cell Biochem 1993;53:314–322.

    CAS  PubMed  Google Scholar 

  90. Flanders KC, Ren RF, Lippa CF. Transforming growth factor-ßs in neurodegenerative disease. Prog Neurobiol 1998;54:71–85.

    CAS  PubMed  Google Scholar 

  91. Unsicker K, Krieglstein K. TGF-betas and their roles in the regulation of neuron survival. Adv Exp Med Biol 2002;513:353–374.

    CAS  PubMed  Google Scholar 

  92. Brionne TC, Tesseur I, Masliah E, Wyss-Coray T. Loss of TGF-β1 leads to increased neuronal cell death and microgliosis in mouse brain. Neuron 2003;40:1133–1145.

    CAS  PubMed  Google Scholar 

  93. Elvers M, Pfeiffer J, Kaltschmidt C, Kaltschmidt B. TGF-β2 neutralization inhibits proliferation and activates apoptosis of cerebellar granule cell precurors in the developing cerebellum. Mech Dev 2005;122:587–602.

    CAS  PubMed  Google Scholar 

  94. Dünker N, Schuster N, Krieglstein K. TGF-β modulates programmed cell death in the retina of the developing chick embryo. Development 2001;128:1933–1942.

    PubMed  Google Scholar 

  95. Krieglstein K, Richter S, Farkas L, et al. Reduction of endogenous transforming growth factors beta prevents ontogenetic neuron death. Nat Neurosci 2000;3:1085–1090.

    CAS  PubMed  Google Scholar 

  96. de Luca MW, Fontana A. TGF-β-induced apoptosis of cerebellar granule neurons is prevented by depolarization. J. Neurosci. 1996;16:4174–4185.

    PubMed  Google Scholar 

  97. Casaccia-Bonnefil P. Cell death in the oligodendrocyte lineage: a molecular perspective of life/death decicisions in development and disease. Glia 2000;29:124–135.

    CAS  PubMed  Google Scholar 

  98. Barres BA, Hart IK, Coles HS, et al. Cell death in the oligodendrocyte lineage. J Neurobiol 1992;23:1221–1230.

    CAS  PubMed  Google Scholar 

  99. Scurlock B, Dawson G. Differential responses of oligodendrocytes to tumor necrosis factor and other pro-apoptotic agents: role of ceramide in apoptosis. J Neurosci Res 1999;55:514–522.

    CAS  PubMed  Google Scholar 

  100. McKinnon RD, Piras G, Ida JA Jr, Dubois-Dalcq M. A role for TGF-β in oligodendrocyte differentiation. J Cell Biol 1993;121:1397–1407.

    CAS  PubMed  Google Scholar 

  101. Schuster N, Bender H, Philippi A, et al. TGF-β induces cell death in the oligodendroglial cell line OLI-neu. Glia 2002;40:95–108.

    PubMed  Google Scholar 

  102. Schuster N, Bender H, Rossler O, et al. Transforming growth factor-beta and tumor necrosis factor-a cooperate to induce apoptosis in the oligodendroglial cell line OLI-new. J Neurosci Res 2003;73:324–333.

    CAS  PubMed  Google Scholar 

  103. Bender H, Wang Z, Schuster N, et al. TIEG1 facilitates transforming growth factor-β-mediated apoptosis in the oligodendroglial cell line OLI-neu. J Neurosci Res 2004;75:344–352.

    CAS  PubMed  Google Scholar 

  104. Ribeiro A, Bronk SF, Roberts PJ, et al. The transforming growth factor beta(1)-inducible transcription factor TIEG1 mediates apoptosis through oxidative stress. Hepatology 1999;30:1490–1497.

    CAS  PubMed  Google Scholar 

  105. Buenemann CL, Willy C, Buchmann A, et al. Transforming growth factor-β1-induced Smad signaling, cell-cycle arrest and apoptosis in hepatoma cells. Carcinogenesis 2001;22:447–452.

    CAS  PubMed  Google Scholar 

  106. Shima Y, Nakao K, Nakashima T, et al. Activation of caspase-8 in transforming growth factor-β-induced apoptosis of human hepatoma cells. Hepatology 1999;30:1215–1222.

    CAS  PubMed  Google Scholar 

  107. Yamamura Y, Hua X, Bergelson S, Lodish HF. Critical role of SMADS and AP-1 complex in transforming growth factor-β-dependent apoptosis. J Biol Chem 2000;275:36,295–36,302.

    CAS  PubMed  Google Scholar 

  108. Landström M, Heldin NE, Bu S, et al. Smad7 mediates apoptosis induced by transforming growth factor β in prostatic carcinoma cells. Curr Biol 2000;10:535–538.

    PubMed  Google Scholar 

  109. Skoff AM, Lisak RP, Bealmear B, Benjamins JA. TNF-alpha and TGF-beta act synergistically to kill Schwann cells. J Neurosci Res 1998;53:747–756.

    CAS  PubMed  Google Scholar 

  110. Yu C, Takeda M, Soliven B. Regulation of cell cycle proteins by TNF-alpha and TGF-beta in cells of oligodendroglial lineage. J Neuroimmunol 2000;108:2–10.

    CAS  PubMed  Google Scholar 

  111. Chipuk JE, Bhat M, Hsing AY, et al. Bcl-xL blocks transforming growth factor-β1-induced apoptosis by inhibiting cytochrome c release and not by directly antagonizing Apaf-1 dependent caspase activation in prostate epithelial cells. J Biol Chem 2001;276:2614–2621.

    Google Scholar 

  112. Saile B, Matthes N, El Armouche H, et al. The bcl, NFkappaB and p53/p21WAF1 systems are involved in spontaneous apoptosis and in the anti-apoptotic effect of TGF-β or TNF-α on activated hepatic stellate cells. Eur J Cell Biol 2001;80:554–561.

    CAS  PubMed  Google Scholar 

  113. Freathy C, Brown DG, Roberts RA, Cain K. Transforming growth factor-β1 induces apoptosis in rat FaO hepatoma cells via cytochrome c release and oligomerization of Apaf-1 to form a 700-kd apoptosome caspase-processing complex. Hepatology 2000;32:750–760.

    CAS  PubMed  Google Scholar 

  114. Zhu Y, Yang GY, Ahlemeyer B, et al. Transforming growth factor-β1 increases Bad phosphorylation and protects neurons against damage. J Neurosci 2002;22:3898–3909.

    CAS  PubMed  Google Scholar 

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  1. Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, The National Institutes of Health, Bethesda, MD, USA

    Tae-Aug Kim PhD & Seong-Jin Kim PhD

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Kim, TA., Kim, SJ. (2008). Mechanisms of TGF-β-Induced Apoptosis in Cancer Cells. In: Transforming Growth Factor-β in Cancer Therapy, Volume I. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-292-2_13

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