NF-кB, a pivotal transcription factor in silica-induced diseases

  • Fei Chen
  • Xianglin Shi
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 37)


Inhalation of silica in a number of occupational settings can result in debilitating and costly lung disease. It is thought that the pathological replacement of functional lung tissue with fibrotic lesions in silica-induced lung disease is the result of chronic inflammation mediated by products of the silica-exposed alveolar macrophage. In particular, inflammatory cytokines, growth factors and reactive oxygen species have been implicated in many acute and chronic inflammatory lung diseases. Pharmacological intervention to modify the production of these mediators has been shown to ameliorate several of these disease processes. Recent studies have demonstrated that the production of these inflammatory mediators is altered as a result of the activation of nuclear factor-KB (NF-KB). NF-KB is a pivotal transcription factor activated by silica in macrophages and other types of lung cells. The understanding of how silica induces NF-KB activation and what signaling pathways are involved in this silica-induced NF-KB activation is important and should provide valuable new information related to both the etiology and potential treatment of silica-related lung diseases. This review summarizes the molecular mechanisms involved in silica-induced NF-KB activation and discusses the importance of NF-KB as a critical transcription factor in mediating silica-induced lung diseases. (Mol Cell Biochem 234/235: 169–176, 2002)

Key words:

silica NF-KB apoptosis cancer 


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  1. 1.
    Chen F, Sun SC, Kuhn DC, Gaydos LJ, Demers LM: Essential role of NF-KB activation in silica-induced inflammatory mediator production in macrophages. Biochem Biophys Res Commun 214: 985–992, 1995PubMedCrossRefGoogle Scholar
  2. 2.
    Chen F, Kuhn DC, Sun SC, Gaydos LJ, Demers LM: Dependence and reversal of nitric oxide production on NF-KB in silica and lipopolysaccharide-induced macrophages. Biochem Biophys Res Commun 214: 839–846, 1995PubMedCrossRefGoogle Scholar
  3. 3.
    Chen F, Castranova V, Shi X, Demers LM: New insights into the role of nuclear factor-KB, a ubiquitous transcription factor in the initiation of diseases. Clin Chem 45: 7–17, 1999PubMedGoogle Scholar
  4. 4.
    Baldwin AS Jr: The NF-KB and IKB proteins: New discoveries and insights. Annu Rev Immunol 14: 649–683, 1996PubMedCrossRefGoogle Scholar
  5. 5.
    Karin M, Delhase M: The IKB kinase [IKK] and NF-KB: Key elements of proinflammatory signalling. Semin Immunol 12: 85–98, 2000PubMedCrossRefGoogle Scholar
  6. 6.
    Karin M, Ben-Neriah Y: Phosphorylation meets ubiquitination: The control of NF-KB activity. Annu Rev Immunol 18: 621–663, 2000PubMedCrossRefGoogle Scholar
  7. 7.
    Mayo MW, Baldwin AS: The transcription factor NF-KB: Control of oncogenesis and cancer therapy resistance. Biochim Biophys Acta 1470: M55–62, 2000PubMedGoogle Scholar
  8. 8.
    Sen R, Baltimore D: Inducibility of K immunoglobulin enhancer-binding protein NF-KB by a posttranslational mechanism. Cell 47: 921–928, 1986PubMedCrossRefGoogle Scholar
  9. 9.
    Kopp EB, Ghosh S: NF-KB and rel proteins in innate immunity. Adv Immunol 58: 1–27, 1995PubMedCrossRefGoogle Scholar
  10. 10.
    Zhang G, Ghosh S: Toll-like receptor-mediated NF-KB activation: A phylogenetically conserved paradigm in innate immunity. J Clin Invest 107: 13–19, 2001PubMedCrossRefGoogle Scholar
  11. 11.
    Chen ZJ, Parent L, Maniatis T: Site-specific phosphorylation of IKBa by a novel ubiquitination-dependent protein kinase activity. Cell 84: 853–862, 1996PubMedCrossRefGoogle Scholar
  12. 12.
    Orian A, Gonen H, Bercovich B, Fajerman I, Eytan E, Israel A, Mercurio F, Iwai K, Schwartz AL, Ciechanover A: SCF-(3-TrCP ubiquitin ligase-mediated processing of NF-KB p105 requires phosphorylation of its C-terminus by IKB kinase. EMBO J 19: 2580–2591, 2000PubMedCrossRefGoogle Scholar
  13. 13.
    Strack P, Caligiuri M, Pelletier M, Boisclair M, Theodoras A, Beer-Romero P, Glass S, Parsons T, Copeland RA, Auger KR, Benfield P, Brizuela L, Rolfe M: SCF-f3-TrCP and phosphorylation dependent ubiquitinationof IKB alpha catalyzed by Ubc3 and Ubc4. Oncogene 19: 3529–3536, 2000PubMedCrossRefGoogle Scholar
  14. 14.
    Neish AS, Gewirtz AT, Zeng H, Young AN, Hobert ME, Karmali V, Rao AS, Madara JL: Prokaryotic regulation of epithelial responses by inhibition of IKBa ubiquitination. Science 289: 1560–1563, 2000PubMedCrossRefGoogle Scholar
  15. 15.
    Palombella VJ, Rando OJ, Goldberg AL, Maniatis T: The ubiquitinproteasome pathway is required for processing the NF-KB1 precursor protein and the activation of NF-KB. Cell 78: 773–785, 1994PubMedCrossRefGoogle Scholar
  16. 16.
    Woronicz JD, Gao X, Cao Z, Rothe M, Goeddel DV: IKB kinase-beta: NF-KB activation and complex formation with IKB kinase-a and NIK. Science 278: 866–869, 1997PubMedCrossRefGoogle Scholar
  17. 17.
    Mercurio F, Zhu H, Murray BW, Shevchenko A, Bennett BL, Li J, Young DB, Barbosa M, Mann M, Manning A, Rao A: IKK-1 and IKK2: Cytokine-activated IKB kinases essential for NF-KB activation. Science 278: 860–866, 1997PubMedCrossRefGoogle Scholar
  18. 18.
    Cohen L, Henzel WJ, Baeuerle PA: IKAP is a scaffold protein of the IKB kinase complex. Nature 395: 292–296, 1998PubMedCrossRefGoogle Scholar
  19. 19.
    Krappmann D, Hatada EN, Tegethoff S, Li J, Klippel A, Giese K, Baeuerle PA, Scheidereit C: The IKB kinase [IKK] complex is tripartite and contains IKK gamma but not IKAP as a regular component. J Biol Chem 275: 29779–29787, 2000PubMedCrossRefGoogle Scholar
  20. 20.
    Leonardi A, Chariot A, Claudio E, Cunningham K, Siebenlist U: CIKS, a connection to IKB kinase and stress-activated protein kinase. Proc Natl Acad Sci USA 97: 10494–10499, 2000PubMedCrossRefGoogle Scholar
  21. 21.
    Li X, Commane M, Nie H, Hua X, Chatterjee-Kishore M, Wald D, Haag M, Stark GR: Actl, an NF-KB-activating protein. Proc Natl Acad Sci USA 97: 10489–10493, 2000PubMedCrossRefGoogle Scholar
  22. 22.
    Hu Y, Baud V, Oga T, Kim KI, Yoshida K, Karin M: IKKa controls formation of the epidermis independently of NF-KB. Nature 410: 710–714, 2001PubMedCrossRefGoogle Scholar
  23. 23.
    Peters RT, Liao SM, Maniatis T: IKKc is part of a novel PMA-inducible IKB kinase complex. Mol Cell 5: 513–522, 2000PubMedCrossRefGoogle Scholar
  24. 24.
    Shimada T, Kawai T, Takeda K, Matsumoto M, Inoue J, Tatsumi Y, Kanamaru A, Akira S: IKK-i, a novel lipopolysaccharide-inducible kinase that is related to IKB kinases. Int Immunol 11: 1357–1362, 1999PubMedCrossRefGoogle Scholar
  25. 25.
    Pomerantz JL, Baltimore D: NF-KB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase. Embo J 18: 6694–6704, 1999PubMedCrossRefGoogle Scholar
  26. 26.
    Israel A: The IKK complex: An integrator of all signals that activate NF-KB? Trends Cell Biol 10: 129–133, 2000PubMedCrossRefGoogle Scholar
  27. 27.
    Tojima Y, Fujimoto A, Delhase M, Chen Y, Hatakeyama S, Nakayama K, Kaneko Y, Nimura Y, Motoyama N, Ikeda K, Karin M, Nakanishi M: NAK is an IKB kinase-activating kinase. Nature 404: 778–782, 2000PubMedCrossRefGoogle Scholar
  28. 28.
    Chen F, Lu Y, Kuhn DC, Maki M, Shi X, Sun SC, Demers LM: Cal-pain contributes to silica-induced IKBa degradation and nuclear factor-kappa B activation. Arch Biochem Biophys 342: 383–388, 1997PubMedCrossRefGoogle Scholar
  29. 29.
    Chen F, Demers LM, Vallyathan V, Lu Y, Castranova V, Shi X: Impairment of NF-KB activation and modulation of gene expression by calpastatin. Am J Physiol Cell Physiol 279: C709–716, 2000PubMedGoogle Scholar
  30. 30.
    Baud V, Liu ZG, Bennett B, Suzuki N, Xia Y, Karin M: Signaling by proinflammatory cytokines: Oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain. Genes Dev 13: 1297–1308, 1999PubMedCrossRefGoogle Scholar
  31. 31.
    Guha M, Mackman N: LPS induction of gene expression in human monocytes. Cell Signal 13: 85–94, 2001PubMedCrossRefGoogle Scholar
  32. 32.
    Carter RS, Geyer BC, Xie M, Acevedo-Suarez CA, Ballard DW: Persistent activation of NF-KB by the tax transforming protein involves chronic phosphorylation of IKB kinase subunits IKK 3 and IKKy. J Biol Chem 26: 26, 2001Google Scholar
  33. 33.
    Jeang K: Functional activities of the human T-cell leukemia virus type I Tax oncoprotein: Cellular signaling through NF-KB. Cytokine Growth Factor Rev 12: 207–217, 2001PubMedCrossRefGoogle Scholar
  34. 34.
    Lin X, Cunningham ET Jr, Mu Y, Geleziunas R, Greene WC: The proto-oncogene Cot kinase participates in CD3/CD28 induction of NF-KB acting through the NF-KB-inducing kinase and IKB kinases. Immunity 10: 271–280, 1999PubMedCrossRefGoogle Scholar
  35. 35.
    Demers LM, Kuhn DC: Influence of mineral dusts on metabolism of arachidonic acid by alveolar macrophage. Environ Health Perspect 102 Suppl 10: 97–100, 1994Google Scholar
  36. 36.
    Huffman LJ, Judy DJ, Castranova V: Regulation of nitric oxide production by rat alveolar macrophages in response to silica exposure. J Toxicol Environ Health A 53: 29–46, 1998PubMedCrossRefGoogle Scholar
  37. 37.
    Davis GS, Pfeiffer LM, Hemenway DR: Persistent overexpression of interleukin-113 and tumor necrosis factor-a in mutine silicosis. J Environ Pathol Toxicol Oncol 17: 99–114, 1998PubMedGoogle Scholar
  38. 38.
    Gosset P, Lassalle P, Vanhee D, Wallaert B, Aerts C, Voisin C, Tonnel AB: Production of tumor necrosis factor-alpha and interleukin-6 by human alveolar macrophages exposed in vitro to coal mine dust. Am J Respir Cell Mol Biol 5: 431–436, 1991PubMedGoogle Scholar
  39. 39.
    Imbert V, Rupec RA, Livolsi A, Pahl HL, Traenckner EB, MuellerDieckmann C, Farahifar D, Rossi B, Auberger P, Baeuerle PA, Peyron JF: Tyrosine phosphorylation of IKBa activates NF-KB without proteolytic degradation of IKBa. Cell 86: 787–798, 1996PubMedCrossRefGoogle Scholar
  40. 40.
    Shi X, Dong Z, Huang C, Ma W, Liu K, Ye J, Chen F, Leonard SS, Ding M, Castranova V, Vallyathan V: The role of hydroxyl radical as a messenger in the activation of nuclear transcription factor NF-KB. Mol Cell Biochem 194: 63–70, 1999PubMedCrossRefGoogle Scholar
  41. 41.
    Shi X, Ding M, Dong Z, Chen F, Ye J, Wang S, Leonard SS, Castranova V, Vallyathan V: Antioxidant properties of aspirin: Characterization of the ability of aspirin to inhibit silica-induced lipid peroxidation, DNA damage, NF-KB activation, and TNFa production. Mol Cell Biochem 199: 93–102, 1999PubMedCrossRefGoogle Scholar
  42. 42.
    Garban HJ, Bonavida B: Nitric oxide disrupts H2O2-dependent activation of nuclear factor icB. Role in sensitization of human tumor cells to tumor necrosis factor-alpha-induced cytotoxicity. J Biol Chem 276: 8918–8923, 2001PubMedCrossRefGoogle Scholar
  43. 43.
    Chen F, Lu Y, Demers LM, Rojanasakul Y, Shi X, Vallyathan V, Castra-nova V: Role of hydroxyl radical in silica-induced NF-KB activation in macrophages. Ann Clin Lab Sci 28: 1–13, 1998PubMedGoogle Scholar
  44. 44.
    Ding M, Shi X, Dong Z, Chen F, Lu Y, Castranova V, Vallyathan V: Freshly fractured crystalline silica induces activator protein-1 activation through ERKs and p38 MAPK. J Biol Chem 274: 30611–30616, 1999PubMedCrossRefGoogle Scholar
  45. 45.
    Shukla A, Timblin CR, Hubbard AK, Bravman J, Mossman BT: Silica-induced activation of c-Jun-NH2-terminal amino kinases, protracted expression of the activator protein-1 proto-oncogene, fra-1, and S-phase alterations are mediated via oxidative stress. Cancer Res 61: 1791–1795, 2001PubMedGoogle Scholar
  46. 46.
    Li N, Karin M: Is NF-KB the sensor of oxidative stress? FASEB J 13: 1137–1143, 1999PubMedGoogle Scholar
  47. 47.
    Han Y, Weinman S, Boldogh I, Walker RK, Brasier AR: Tumor necrosis factor-a-inducible IKBa proteolysis mediated by cytosolic m-calpain. A mechanism parallel to the ubiquitin-proteasome pathway for nuclear factor-KB activation. J Biol Chem 274: 787–794, 1999PubMedCrossRefGoogle Scholar
  48. 48.
    Baghdiguian S, Martin M, Richard I, Pons F, Astier C, Bourg N, Hay RT, Chemaly R, Halaby G, Loiselet J, Anderson LV, Lopez de Munain A, Fardeau M, Mangeat P, Beckmann JS, Lefranc G: Calpain 3 deficiency is associated with myonuclear apoptosis and profound perturbation of the IKBa/NF-KB pathway in limb-girdle muscular dystrophy type 2A. Nat Med 5: 503–511, 1999PubMedCrossRefGoogle Scholar
  49. 49.
    Miyamoto S, Seufzer BJ, Shumway SD: Novel IKBa proteolytic pathway in WEHI231 immature B cells. Mol Cell Biol 18: 19–29, 1998PubMedGoogle Scholar
  50. 50.
    Shumway SD, Maki M, Miyamoto S: The PEST domain of IKBa is necessary and sufficient for in vitro degradation by.t-calpain. J Biol Chem 274: 30874–30881, 1999PubMedCrossRefGoogle Scholar
  51. 51.
    Wang KK, Yuen PW: Calpain inhibition: An overview of its therapeutic potential. Trends Pharmacol Sci 15: 412–419, 1994PubMedCrossRefGoogle Scholar
  52. 52.
    Potter DA, Timauer JS, Janssen R, Croall DE, Hughes CN, Fiacco KA, Mier JW, Maki M, Herman IM: Calpain regulates actin remodeling during cell spreading. J Cell Biol 141: 647–662, 1998PubMedCrossRefGoogle Scholar
  53. 53.
    Tanabe F, Cui SH, Ito M: Ceramide promotes calpain-mediated proteolysis of protein kinase C13 in mutine polymorphonuclear leukocytes. Biochem Biophys Res Commun 242: 129–133, 1998PubMedCrossRefGoogle Scholar
  54. 54.
    Kavita U, Mizel SB: Differential sensitivity of interleukin-1a and -13 precursor proteins to cleavage by calpain, a calcium-dependent protease. J Biol Chem 270: 27758–27765, 1995PubMedCrossRefGoogle Scholar
  55. 55.
    Gonen H, Shkedy D, Bamoy S, Kosower NS, Ciechanover A: On the involvement of calpains in the degradation of the tumor suppressor protein p53. FEBS Lett 406: 17–22, 1997PubMedCrossRefGoogle Scholar
  56. 56.
    Kubbutat MH, Vousden KH: Proteolytic cleavage of human p53 by calpain: A potential regulator of protein stability. Mol Cell Biol 17: 460–468, 1997PubMedGoogle Scholar
  57. 57.
    Pariat M, Carillo S, Molinari M, Salvat C, Debussche L, Bracco L, Milner J, Piechaczyk M: Proteolysis by calpains: A possible contribution to degradation of p53. Mol Cell Biol 17: 2806–2815, 1997PubMedGoogle Scholar
  58. 58.
    Zhang W, Lu Q, Xie ZJ, Mellgren RL: Inhibition of the growth of WI-38 fibroblasts by benzyloxycarbonyl-Leu-Leu-Tyr diazomethyl ketone: Evidence that cleavage of p53 by a calpain-like protease is necessary for GI to S-phase transition. Oncogene 14: 255–263, 1997PubMedCrossRefGoogle Scholar
  59. 59.
    Balcerzak D, Cottin P, Poussard S, Cucuron A, Brustis JJ, Ducastaing A: Calpastatin-modulation of m-calpain activity is required for myoblast fusion. Eur J Cell Biol 75: 247–253, 1998PubMedCrossRefGoogle Scholar
  60. 60.
    McDonald AD, McDonald JC, Rando RJ, Hughes JM, Weill H: Cohort mortality study of North American industrial sand workers. I. Mortality from lung cancer, silicosis and other causes. Ann Occup Hyg 45: 193–139, 2001PubMedGoogle Scholar
  61. 61.
    Steenland K, Sanderson W: Lung cancer among industrial sand workers exposed to crystalline silica. Am J Epidemiol 153: 695–703, 2001PubMedCrossRefGoogle Scholar
  62. 62.
    Hessel PA, Gamble JF, Gee JB, Gibbs G, Green FH, Morgan WK, Mossman BT: Silica, silicosis, and lung cancer: A response to a recent working group report. J Occup Environ Med 42: 704–720, 2000PubMedCrossRefGoogle Scholar
  63. 63.
    Cherry NM, Burgess GL, Turner S, McDonald JC: Crystalline silica and risk of lung cancer in the potteries. Occup Environ Med 55: 779–785, 1998PubMedCrossRefGoogle Scholar
  64. 64.
    Checkoway H, Franzblau A: Is silicosis required for silica-associated lung cancer? Am J Ind Med 37: 252–259, 2000PubMedCrossRefGoogle Scholar
  65. 65.
    Bours V, Bentires-Alj M, Hellin AC, Viatour P, Robe P, Delhalle S, Benoit V, Merville MP: Nuclear factor-KB, cancer, and apoptosis. Biochem Pharmacol 60: 1085–1089, 2000PubMedCrossRefGoogle Scholar
  66. 66.
    Fausto N, Laird AD, Webber EM: Liver regeneration. 2. Role of growth factors and cytokines in hepatic regeneration. FASEB J 9: 1527–1536, 1995PubMedGoogle Scholar
  67. 67.
    Beg AA, Sha WC, Bronson RT, Ghosh S, Baltimore D: Embryonic lethality and liver degeneration in mice lacking the ReIA component of NF-KB. Nature 376: 167–170, 1995PubMedCrossRefGoogle Scholar
  68. 68.
    Wang CY, Mayo MW, Komeluk RG, Goeddel DV, Baldwin AS Jr: NF-KB antiapoptosis: Induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 281: 1680–1683, 1998PubMedCrossRefGoogle Scholar
  69. 69.
    Stehlik C, de Martin R, Kumabashiri I, Schmid JA, Binder BR, Lipp J: Nuclear factor NF-KB-regulated X-chromosome-linked iap gene expression protects endothelial cells from tumor necrosis factor alpha-induced apoptosis. J Exp Med 188: 211–216, 1998PubMedCrossRefGoogle Scholar
  70. 70.
    Wu MX, Ao Z, Prasad KV, Wu R, Schlossman SF: IEX-1L, an apoptosis inhibitor involved in NF-KB-mediated cell survival. Science 281: 998–1001, 1998PubMedCrossRefGoogle Scholar
  71. 71.
    Chen F, Demers LM, Vallyathan V, Lu Y, Castranova V, Shi X: Involvement of 5’-flanking KB-like sites within bel-x gene in silica-induced Bel-x expression. J Biol Chem 274: 35591–35595, 1999PubMedCrossRefGoogle Scholar
  72. 72.
    Lee HH, Dadgostar H, Cheng Q, Shu J, Cheng G: NF-KB-mediated up-regulation of Bel-x and Bfl-1/A1 is required for CD40 survival signaling in B lymphocytes. Proc Natl Acad Sci USA 96: 9136–9141, 1999PubMedCrossRefGoogle Scholar
  73. 73.
    Sarnia V, Lin Z, Clark L, Rust BM, Tewari M, Noelle RJ, Dixit VM: Activation of the B-cell surface receptor CD40 induces A20, a novel zinc finger protein that inhibits apoptosis. J Biol Chem 270: 12343–12346, 1995CrossRefGoogle Scholar
  74. 74.
    Hinz M, Loser P, Mathas S, Krappmann D, Dorken B, Scheidereit C: Constitutive NF-KB maintains high expression of a characteristic genenetwork, including CD40, CD86, and a set of antiapoptotic genes in Hodgkin/Reed-Sternberg cells. Blood 97: 2798–2807, 2001PubMedCrossRefGoogle Scholar
  75. 75.
    Boise LH, Gonzalez-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nunez G, Thompson CB: Bel-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell 74: 597–608, 1993Google Scholar
  76. 76.
    Fang W, Weintraub BC, Dunlap B, Garside P, Pape KA, Jenkins MK, Goodnow CC, Mueller DL, Behrens TW: Self-reactive B lymphocytes overexpressing Bcl-xL escape negative selection and are tolerized by clonal anergy and receptor editing. Immunity 9: 35–45, 1998PubMedCrossRefGoogle Scholar
  77. 77.
    Okada S, Zhang H, Hatano M, Tokuhisa T: A physiologic role of BelxL induced in activated macrophages. J Immunol 160: 2590–2596, 1998PubMedGoogle Scholar
  78. 78.
    Xerri L, Parc P, Brousset P, Schlaifer D, Hassoun J, Reed JC, Krajewski S, Birnbaum D: Predominant expression of the long isoform of Bcl-x [Bcl-xL] in human lymphomas. Br J Haematol 92: 900–906, 1996CrossRefGoogle Scholar
  79. 79.
    Bargou RC, Daniel PT, Mapara MY, Bommert K, Wagener C, Kallinich B, Royer HD, Dorken B: Expression of the bel-2 gene family in normal and malignant breast tissue: Low bax-a expression in tumor cells correlates with resistance towards apoptosis. Int J Cancer 60: 854–859, 1995PubMedCrossRefGoogle Scholar
  80. 80.
    Hanahan D, Weinberg RA: The hallmarks of cancer. Cell 100: 57–70, 2000PubMedCrossRefGoogle Scholar
  81. 81.
    Wadgaonkar R, Phelps KM, Hague Z, Williams AJ, Silverman ES, Collins T: CREB-binding protein is a nuclear integrator of nuclear factor-KB and p53 signaling. J Biol Chem 274: 1879–1882, 1999PubMedCrossRefGoogle Scholar
  82. 82.
    Yang JP, Hori M, Takahashi N, Kawabe T, Kato H, Okamoto T: NF-KB subunit p65 binds to 53BP2 and inhibits cell death induced by 53BP2. Oncogene 18: 5177–5186, 1999PubMedCrossRefGoogle Scholar
  83. 83.
    Shao J, Fujiwara T, Kadowaki Y, Fukazawa T, Waku T, Itoshima T, Yamatsuji T, Nishizaki M, Roth JA, Tanaka N: Overexpression of the wild-type p53 gene inhibits NF-KB activity and synergizes with aspirin to induce apoptosis in human colon cancer cells. Oncogene 19: 726–736, 2000PubMedCrossRefGoogle Scholar
  84. 84.
    Joyce D, Bouzahzah B, Fu M, Albanese C, D’Amico M, Steer J, Klein JU, Lee RJ, Segall JE, Westwick JK, Der CJ, Pestell RG: Integration of Rac-dependent regulation of cyclin D1 transcription through a nuclear factor-KB-dependent pathway. J Biol Chem 274: 25245–25249, 1999PubMedCrossRefGoogle Scholar
  85. 85.
    Guttridge DC, Albanese C, Reuther JY, Pestell RG, Baldwin AS Jr: NF-KB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol Cell Biol 19: 5785–5799, 1999PubMedGoogle Scholar
  86. 86.
    Schwartz SA, Hernandez A, Mark Evers B: The role of NF-KB/IKB proteins in cancer: Implications for novel treatment strategies. Surg Oncol 8: 143–153, 1999PubMedCrossRefGoogle Scholar
  87. 87.
    Baldwin AS: Control of oncogenesis and cancer therapy resistance by the transcription factor NF-KB. J Clin Invest 107: 241–246, 2001PubMedCrossRefGoogle Scholar
  88. 88.
    Wang CY, Cusack JC Jr, Liu R, Baldwin AS Jr: Control of inducible chemoresistance: Enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-KB. Nat Med 5: 412–417, 1999PubMedCrossRefGoogle Scholar
  89. 89.
    Ant A, Vorndamm J, Breitenbroich M, Folsch UR, Kalthoff H, Schmidt WE, Schafer H: Inhibition of NF-KB sensitizes human pancreatic carcinoma cells to apoptosis induced by etoposide [VP16] or doxorubicin. Oncogene 20: 859–868, 2001CrossRefGoogle Scholar
  90. 90.
    Jones DR, Broad RM, Madrid LV, Baldwin AS Jr, Mayo MW: Inhibition of NF-KB sensitizes non-small cell lung cancer cells to chemotherapy-induced apoptosis. Ann Thorac Surg 70: 930–936; discussion 936–937, 2000PubMedCrossRefGoogle Scholar
  91. 91.
    Kato T, Duffey DC, Ondrey FG, Dong G, Chen Z, Cook JA, Mitchell JB, Van Waes C: Cisplatin and radiation sensitivity in human head and neck squamous carcinomas are independently modulated by glutathione and transcription factor NF-KB. Head Neck 22: 748–759, 2000PubMedCrossRefGoogle Scholar
  92. 92.
    Romano MF, Lamberti A, Bisogni R, Tassone P, Pagnini D, Storti G, Del Vecchio L, Turco MC, Venuta S: Enhancement of cytosine arabinoside-induced apoptosis in human myeloblastic leukemia cells by NF-KB/Rel-specific decoy oligodeoxynucleotides. Gene Ther 7: 1234–1237, 2000PubMedCrossRefGoogle Scholar
  93. 93.
    Cusack JC Jr, Liu R, Baldwin AS Jr: Inducible chemoresistance to 7-ethyl-1044-[1-piperidino]-1-piperidino]-carbonyloxycamptothecin [CPT-I1] in colorectal cancer cells and a xenograft model is overcome by inhibition of nuclear factor-kB activation. Cancer Res 60: 2323–2330, 2000PubMedGoogle Scholar
  94. 94.
    Sumitomo M, Tachibana M, Ozu C, Asakura H, Murai M, Hayakawa M, Nakamura H, Takayanagi A, Shimizu N: Induction of apoptosis of cytokine-producing bladder cancer cells by adenovirus-mediated IxBa overexpression. Hum Gene Ther 10: 37–47, 1999PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Fei Chen
    • 1
  • Xianglin Shi
    • 1
  1. 1.The Health Effects Laboratory DivisionNational Institute for Occupational Safety and HealthMorgantownUSA

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