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Role of nuclear factor-κ B in melanoma

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Abstract

Nuclear Factor-kappa B (NF-κ B) is an inducible transcription factor that regulates the expression of many genes involved in the immune response. Recently, NF-κ B activity has been shown to be upregulated in many cancers, including melanoma. Data indicate that the enhanced activation of NF-κ B may be due to deregulations in upstream signaling pathways such as Ras/Raf, PI3K/Akt, and NIK. Multiple studies have shown that NF-κ B is involved in the regulation of apoptosis, angiogenesis, and tumor cell invasion, all of which indicate the important role of NF-κ B in tumorigenesis. Thus, understanding the molecular mechanism of melanoma progression will aid in designing new therapeutic approaches for melanoma. In this review, the association between NF-κ B and melanoma tumorigenesis are discussed. Additionally, the potential of emerging selective NF-κ B inhibitors for the treatment of melanoma is reviewed.

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References

  1. Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ: Cancer statistics, 2003. CA Cancer J Clin 53: 5–26, 2003

    Google Scholar 

  2. Oliveria S, Dusza S, Berwick M: Issues in the epidemiology of melanoma. Expert Rev Anticancer Ther 1: 453–459, 2001

    Google Scholar 

  3. Clark WH: Tumour progression and the nature of cancer. Br J Cancer 64: 631–644, 1991

    Google Scholar 

  4. Sun W, Schuchter LM: Metastatic melanoma. Curr Treat Options Oncol 2: 193–202, 2001

    Google Scholar 

  5. Balch CM, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG, Fleming ID, Gershenwald JE, Houghton A, Jr., Kirkwood JM, McMasters KM, Mihm MF, Morton DL, Reintgen DS, Ross MI, Sober A, Thompson JA, Thompson JF: Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 19: 3635–3648, 2001

    Google Scholar 

  6. Punt CJ, Eggermont AM: Adjuvant interferon-alpha for melanoma revisited: News from old and new studies. Ann Oncol 12: 1663–1666, 2001

    Google Scholar 

  7. Ivanov VN, Bhoumik A, Ronai Z: Death receptors and melanoma resistance to apoptosis. Oncogene 22: 3152–3161, 2003

    Google Scholar 

  8. Nyormoi O, Bar-Eli M: Transcriptional regulation of metastasis-related genes in human melanoma. Clin Exp Metastasis 20: 251–263, 2003

    Google Scholar 

  9. Wang W, Abbruzzese JL, Evans DB, Larry L, Cleary KR, Chiao PJ: The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells. Clin Cancer Res 5: 119–127, 1999

    Google Scholar 

  10. Bours V, Dejardin E, Goujon-Letawe F, Merville MP, Castronovo V: The NF-kappa B transcription factor and cancer: High expression of NF-kappa B- and I kappa B-related proteins in tumor cell lines. Biochem Pharmacol 47: 145–149, 1994

    Google Scholar 

  11. Sovak MA, Bellas RE, Kim DW, Zanieski GJ, Rogers AE, Traish AM, Sonenshein GE: Aberrant nuclear factor-kappaB/Rel expression and the pathogenesis of breast cancer. J Clin Invest 100: 2952–2960, 1997

    Google Scholar 

  12. Dejardin E, Bonizzi G, Bellahcene A, Castronovo V, Merville MP, Bours V: Highly-expressed p100/p52 (NFKB2) sequesters other NF-kappa B-related proteins in the cytoplasm of human breast cancer cells. Oncogene 11: 1835–1841, 1995

    Google Scholar 

  13. Duffey DC, Chen Z, Dong G, Ondrey FG, Wolf JS, Brown K, Siebenlist U, Van Waes C: Expression of a dominant-negative mutant inhibitor-kappaBalpha of nuclear factor-kappaB in human head and neck squamous cell carcinoma inhibits survival, proinflammatory cytokine expression, and tumor growth in vivo. Cancer Res 59: 3468–3474, 1999

    Google Scholar 

  14. Nakshatri H, Bhat-Nakshatri P, Martin DA, Goulet RJ, Jr., Sledge GW, Jr.: Constitutive activation of NF-kappaB during progression of breast cancer to hormone-independent growth. Mol Cell Biol 17: 3629–3639, 1997

    Google Scholar 

  15. Abraham E: NF-kappaB activation. Crit Care Med 28: N100–104, 2000

    Google Scholar 

  16. Beg AA, Ruben SM, Scheinman RI, Haskill S, Rosen CA, Baldwin AS, Jr.: I kappa B interacts with the nuclear localization sequences of the subunits of NF-kappa B: A mechanism for cytoplasmic retention. Genes Dev 6: 1899–1913, 1992

    Google Scholar 

  17. Makarov SS: NF-kappaB as a therapeutic target in chronic inflammation: Recent advances. Mol Med Today 6: 441–448, 2000

    Google Scholar 

  18. Chen FE, Ghosh G: Regulation of DNA binding by Rel/NF-kappaB transcription factors: Structural views. Oncogene 18: 6845–6852, 1999

    Google Scholar 

  19. Baldwin AS: Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB. J Clin Invest 107: 241–246, 2001

    Google Scholar 

  20. McNulty SE, Tohidian NB, Meyskens FL, Jr.: RelA, p50 and inhibitor of kappa B alpha are elevated in human metastatic melanoma cells and respond aberrantly to ultraviolet light B. Pigment Cell Res 14: 456–465, 2001

    Google Scholar 

  21. Dhawan P, Richmond A: A novel NF-kappa B-inducing kinase-MAPK signaling pathway up-regulates NF-kappa B activity in melanoma cells. J Biol Chem 277: 7920–7928, 2002

    Google Scholar 

  22. McNulty SE, del Rosario R, Cen D, Meyskens FL, Jr., Yang S: Comparative expression of NF-kappaB proteins in melanocytes of normal skin vs. benign intradermal naevus and human metastatic melanoma biopsies. Pigment Cell Res 17: 173–180, 2004

    Google Scholar 

  23. Deveraux QL, Roy N, Stennicke HR, Van Arsdale T, Zhou Q, Srinivasula SM, Alnemri ES, Salvesen GS, Reed JC: IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. Embo J 17: 2215–2223, 1998

    Google Scholar 

  24. Wang CY, Mayo MW, Korneluk RG, Goeddel DV, Baldwin AS, Jr.: NF-kappaB antiapoptosis: Induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 281: 1680–1683, 1998

    Google Scholar 

  25. Baldwin AS, Jr.: The NF-kappa B and I kappa B proteins: New discoveries and insights. Annu Rev Immunol 14: 649–683, 1996

    Google Scholar 

  26. Micheau O, Lens S, Gaide O, Alevizopoulos K, Tschopp J: NF-kappaB signals induce the expression of c-FLIP. Mol Cell Biol 21: 5299–5305, 2001

    Google Scholar 

  27. Ravi R, Bedi GC, Engstrom LW, Zeng Q, Mookerjee B, Gelinas C, Fuchs EJ, Bedi A: Regulation of death receptor expression and TRAIL/Apo2L-induced apoptosis by NF-kappaB. Nat Cell Biol 3: 409–416, 2001

    Google Scholar 

  28. Catz SD, Johnson JL: Transcriptional regulation of bcl-2 by nuclear factor kappa B and its significance in prostate cancer. Oncogene 20: 7342–7351, 2001

    Google Scholar 

  29. Grossman D, McNiff JM, Li F, Altieri DC: Expression and targeting of the apoptosis inhibitor, survivin, in human melanoma. J Invest Dermatol 113: 1076–1081, 1999

    Google Scholar 

  30. Vucic D, Stennicke HR, Pisabarro MT, Salvesen GS, Dixit VM: ML-IAP, a novel inhibitor of apoptosis that is preferentially expressed in human melanomas. Curr Biol 10: 1359–1366, 2000

    Google Scholar 

  31. Alonso SR, Ortiz P, Pollan M, Perez-Gomez B, Sanchez L, Acuna MJ, Pajares R, Martinez-Tello FJ, Hortelano CM, Piris MA, Rodriguez-Peralto JL: Progression in cutaneous malignant melanoma is associated with distinct expression profiles: A tissue microarray-based study. Am J Pathol 164: 193–203, 2004

    Google Scholar 

  32. Franco AV, Zhang XD, Van Berkel E, Sanders JE, Zhang XY, Thomas WD, Nguyen T, Hersey P: The role of NF-kappa B in TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of melanoma cells. J Immunol 166: 5337–5345, 2001

    Google Scholar 

  33. Ivanov VN, Fodstad O, Ronai Z: Expression of ring finger-deleted TRAF2 sensitizes metastatic melanoma cells to apoptosis via up-regulation of p38, TNFalpha and suppression of NF-kappaB activities. Oncogene 20: 2243–2253, 2001

    Google Scholar 

  34. Bakker TR, Reed D, Renno T, Jongeneel CV: Efficient adenoviral transfer of NF-kappaB inhibitor sensitizes melanoma to tumor necrosis factor-mediated apoptosis. Int J Cancer 80: 320–323, 1999

    Google Scholar 

  35. Wang D, Yang W, Du J, Devalaraja MN, Liang P, Matsumoto K, Tsubakimoto K, Endo T, Richmond A: MGSA/GRO-mediated melanocyte transformation involves induction of Ras expression. Oncogene 19: 4647–4659, 2000

    Google Scholar 

  36. Guttridge DC, Albanese C, Reuther JY, Pestell RG, Baldwin AS, Jr.: NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol Cell Biol 19: 5785–5799, 1999

    Google Scholar 

  37. Hinz M, Krappmann D, Eichten A, Heder A, Scheidereit C, Strauss M: NF-kappaB function in growth control: Regulation of cyclin D1 expression and G0/G1-to-S-phase transition. Mol Cell Biol 19: 2690–2698, 1999

    Google Scholar 

  38. Bash J, Zong WX, Gelinas C: c-Rel arrests the proliferation of HeLa cells and affects critical regulators of the G1/S-phase transition. Mol Cell Biol 17: 6526–6536, 1997

    Google Scholar 

  39. Yang J, Richmond A: Constitutive IkappaB kinase activity correlates with nuclear factor-kappaB activation in human melanoma cells. Cancer Res 61: 4901–4909, 2001

    Google Scholar 

  40. Kunz M, Hartmann A, Flory E, Toksoy A, Koczan D, Thiesen HJ, Mukaida N, Neumann M, Rapp UR, Brocker EB, Gillitzer R: Anoxia-induced up-regulation of interleukin-8 in human malignant melanoma. A potential mechanism for high tumor aggressiveness. Am J Pathol 155: 753–763, 1999

    Google Scholar 

  41. Luca M, Huang S, Gershenwald JE, Singh RK, Reich R, Bar-Eli M: Expression of interleukin-8 by human melanoma cells up-regulates MMP-2 activity and increases tumor growth and metastasis. Am J Pathol 151: 1105–1113, 1997

    Google Scholar 

  42. Rofstad EK, Halsor EF: Vascular endothelial growth factor, interleukin 8, platelet-derived endothelial cell growth factor, and basic fibroblast growth factor promote angiogenesis and metastasis in human melanoma xenografts. Cancer Res 60: 4932–4938, 2000

    Google Scholar 

  43. Kashani-Sabet M, Shaikh L, Miller JR, 3rd, Nosrati M, Ferreira CM, Debs RJ, Sagebiel RW: NF-kappa B in the vascular progression of melanoma. J Clin Oncol 22: 617–623, 2004

    Google Scholar 

  44. Denkert C, Kobel M, Berger S, Siegert A, Leclere A, Trefzer U, Hauptmann S: Expression of cyclooxygenase 2 in human malignant melanoma. Cancer Res 61: 303–308, 2001

    Google Scholar 

  45. Goulet AC, Einsphar JG, Alberts DS, Beas A, Burk C, Bhattacharyya A, Bangert J, Harmon JM, Fujiwara H, Koki A, Nelson MA: Analysis of cyclooxygenase 2 (COX-2) expression during malignant melanoma progression. Cancer Biol Ther 2: 713–718, 2003

    Google Scholar 

  46. van de Stolpe A, Caldenhoven E, Stade BG, Koenderman L, Raaijmakers JA, Johnson JP, van der Saag PT: 12-O-tetradecanoylphorbol-13-acetate- and tumor necrosis factor alpha-mediated induction of intercellular adhesion molecule-1 is inhibited by dexamethasone. Functional analysis of the human intercellular adhesion molecular-1 promoter. J Biol Chem 269: 6185–6192, 1994

    Google Scholar 

  47. Iademarco MF, McQuillan JJ, Rosen GD, Dean DC: Characterization of the promoter for vascular cell adhesion molecule-1 (VCAM-1). J Biol Chem 267: 16323–16329, 1992

    Google Scholar 

  48. Whelan J, Ghersa P, Hooft van Huijsduijnen R, Gray J, Chandra G, Talabot F, DeLamarter JF: An NF kappa B-like factor is essential but not sufficient for cytokine induction of endothelial leukocyte adhesion molecule 1 (ELAM-1) gene transcription. Nucleic Acids Res 19: 2645–2653, 1991

    Google Scholar 

  49. Borghaei RC, Rawlings PL, Jr., Javadi M, Woloshin J: NF-kappaB binds to a polymorphic repressor element in the MMP-3 promoter. Biochem Biophys Res Commun 316: 182–188, 2004

    Google Scholar 

  50. Bond M, Fabunmi RP, Baker AH, Newby AC: Synergistic upregulation of metalloproteinase-9 by growth factors and inflammatory cytokines: An absolute requirement for transcription factor NF-kappa B. FEBS Lett 435: 29–34, 1998

    Google Scholar 

  51. Johnson JP, Stade BG, Holzmann B, Schwable W, Riethmuller G: De novo expression of intercellular-adhesion molecule-1 in melanoma correlates with increased risk of metastasis. Proc Natl Acad Sci USA 86: 641–644, 1989

    Google Scholar 

  52. Boyano MD, Garcia-Vazquez MD, Lopez-Michelena T, Gardeazabal J, Bilbao J, Canavate ML, Galdeano AG, Izu R, Diaz-Ramon L, Raton JA, Diaz-Perez JL: Soluble interleukin-2 receptor, intercellular adhesion molecule-1 and interleukin-10 serum levels in patients with melanoma. Br J Cancer 83: 847–852, 2000

    Google Scholar 

  53. Hirai S, Kageshita T, Kimura T, Tsujisaki M, Imai K, Wakamatsu K, Ito S, Ono T: Serum levels of sICAM-1 and 5-S-cysteinyldopa as markers of melanoma progression. Melanoma Res 7: 58–62, 1997

    Google Scholar 

  54. Langley RR, Carlisle R, Ma L, Specian RD, Gerritsen ME, Granger DN: Endothelial expression of vascular cell adhesion molecule-1 correlates with metastatic pattern in spontaneous melanoma. Microcirculation 8: 335–345, 2001

    Google Scholar 

  55. Biancone L, Araki M, Araki K, Vassalli P, Stamenkovic I: Redirection of tumor metastasis by expression of E-selectin in vivo. J Exp Med 183: 581–587, 1996

    Google Scholar 

  56. van den Oord JJ, Paemen L, Opdenakker G, de Wolf-Peeters C: Expression of gelatinase B and the extracellular matrix metalloproteinase inducer EMMPRIN in benign and malignant pigment cell lesions of the skin. Am J Pathol 151: 665–670, 1997

    Google Scholar 

  57. 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-kappaB. Nat Med 5: 412–417, 1999

    Google Scholar 

  58. Kuo MT, Liu Z, Wei Y, Lin-Lee YC, Tatebe S, Mills GB, Unate H: Induction of human MDR1 gene expression by 2-acetylaminofluorene is mediated by effectors of the phosphoinositide 3-kinase pathway that activate NF-kappaB signaling. Oncogene 21: 1945–1954, 2002

    Google Scholar 

  59. Deng L, Lin-Lee YC, Claret FX, Kuo MT: 2-acetylaminofluorene up-regulates rat mdr1b expression through generating reactive oxygen species that activate NF-kappa B pathway. J Biol Chem 276: 413–420, 2001

    Google Scholar 

  60. Zhou G, Kuo MT: NF-kappaB-mediated induction of mdr1b expression by insulin in rat hepatoma cells. J Biol Chem 272: 15174–15183, 1997

    Google Scholar 

  61. Um JH, Kang CD, Lee BG, Kim DW, Chung BS, Kim SH: Increased and correlated nuclear factor-kappa B and Ku autoantigen activities are associated with development of multidrug resistance. Oncogene 20: 6048–6056, 2001

    Google Scholar 

  62. Tamatani T, Azuma M, Aota K, Yamashita T, Bando T, Sato M: Enhanced IkappaB kinase activity is responsible for the augmented activity of NF-kappaB in human head and neck carcinoma cells. Cancer Lett 171: 165–172, 2001

    Google Scholar 

  63. Mukhopadhyay T, Roth JA, Maxwell SA: Altered expression of the p50 subunit of the NF-kappa B transcription factor complex in non-small cell lung carcinoma. Oncogene 11: 999–1003, 1995

    Google Scholar 

  64. Shattuck-Brandt RL, Richmond A: Enhanced degradation of I-kappaB alpha contributes to endogenous activation of NF-kappaB in Hs294T melanoma cells. Cancer Res 57: 3032–3039, 1997

    Google Scholar 

  65. Shattuck RL, Wood LD, Jaffe GJ, Richmond A: MGSA/GRO transcription is differentially regulated in normal retinal pigment epithelial and melanoma cells. Mol Cell Biol 14: 791–802, 1994

    Google Scholar 

  66. Wood LD, Farmer AA, Richmond A: HMGI(Y) and Sp1 in addition to NF-kappa B regulate transcription of the MGSA/GRO alpha gene. Nucleic Acids Res 23: 4210–4219, 1995

    Google Scholar 

  67. Wood LD, Richmond A: Constitutive and cytokine-induced expression of the melanoma growth stimulatory activity/GRO alpha gene requires both NF-kappa B and novel constitutive factors. J Biol Chem 270: 30619–30626, 1995

    Google Scholar 

  68. Kondo S, Kono T, Sauder DN, McKenzie RC: IL-8 gene expression and production in human keratinocytes and their modulation by UVB. J Invest Dermatol 101: 690–694, 1993

    Google Scholar 

  69. Wang Y, Becker D: Antisense targeting of basic fibroblast growth factor and fibroblast growth factor receptor-1 in human melanomas blocks intratumoral angiogenesis and tumor growth. Nat Med 3: 887–893, 1997

    Google Scholar 

  70. Shih IM, Herlyn M: Autocrine and paracrine roles for growth factors in melanoma. In Vivo 8: 113–123, 1994

    Google Scholar 

  71. Gilmore TD, Koedood M, Piffat KA, White DW: Rel/NF-kappaB/IkappaB proteins and cancer. Oncogene 13: 1367–1378, 1996

    Google Scholar 

  72. Karin M, Lin A: NF-kappaB at the crossroads of life and death. Nat Immunol 3: 221–227, 2002

    Google Scholar 

  73. Pando MP, Verma IM: Signal-dependent and -independent degradation of free and NF-kappa B-bound IkappaBalpha. J Biol Chem 275: 21278–21286, 2000

    Google Scholar 

  74. Devalaraja MN, Wang DZ, Ballard DW, Richmond A: Elevated constitutive IkappaB kinase activity and IkappaB-alpha phosphorylation in Hs294T melanoma cells lead to increased basal MGSA/GRO-alpha transcription. Cancer Res 59: 1372–1377, 1999

    Google Scholar 

  75. Sizemore N, Lerner N, Dombrowski N, Sakurai H, Stark GR: Distinct roles of the Ikappa B kinase alpha and beta subunits in liberating nuclear factor kappa B (NF-kappa B) from Ikappa B and in phosphorylating the p65 subunit of NF-kappa B. J Biol Chem 277: 3863–3869, 2002

    Google Scholar 

  76. Ling L, Cao Z, Goeddel DV: NF-kappaB-inducing kinase activates IKK-alpha by phosphorylation of Ser-176. Proc Natl Acad Sci USA 95: 3792–3797, 1998

    Google Scholar 

  77. Nakano H, Shindo M, Sakon S, Nishinaka S, Mihara M, Yagita H, Okumura K: Differential regulation of IkappaB kinase alpha and beta by two upstream kinases, NF-kappaB-inducing kinase and mitogen-activated protein kinase/ERK kinase kinase-1. Proc Natl Acad Sci USA 95: 3537–3542, 1998

    Google Scholar 

  78. Smith C, Andreakos E, Crawley JB, Brennan FM, Feldmann M, Foxwell BM: NF-kappaB-inducing kinase is dispensable for activation of NF-kappaB in inflammatory settings but essential for lymphotoxin beta receptor activation of NF-kappaB in primary human fibroblasts. J Immunol 167: 5895–5903, 2001

    Google Scholar 

  79. Malinin NL, Boldin MP, Kovalenko AV, Wallach D: MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1. Nature 385: 540–544, 1997

    Google Scholar 

  80. Xiao G, Harhaj EW, Sun SC: NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100. Mol Cell 7: 401–409, 2001

    Google Scholar 

  81. Cogswell PC, Guttridge DC, Funkhouser WK, Baldwin AS, Jr.: Selective activation of NF-kappa B subunits in human breast cancer: Potential roles for NF-kappa B2/p52 and for Bcl-3. Oncogene 19: 1123–1131, 2000

    Google Scholar 

  82. Li X, Stark GR: NF-kappaB-dependent signaling pathways. Exp Hematol 30: 285–296, 2002

    Google Scholar 

  83. Delhase M, Li N, Karin M: Kinase regulation in inflammatory response. Nature 406: 367–368, 2000

    Google Scholar 

  84. Koul D, Yao Y, Abbruzzese JL, Yung WK,Reddy SA: Tumor suppressor MMAC/PTEN inhibits cytokine-induced NF-kappaB activation without interfering with the IkappaB degradation pathway. J Biol Chem 276: 11402–11408, 2001

    Google Scholar 

  85. Madrid LV, Mayo MW, Reuther JY, Baldwin AS, Jr.: Akt stimulates the transactivation potential of the RelA/p65 Subunit of NF-kappa B through utilization of the Ikappa B kinase and activation of the mitogen-activated protein kinase p38. J Biol Chem 276: 18934–18940, 2001

    Google Scholar 

  86. Dhawan P, Singh AB, Ellis DL, Richmond A: Constitutive activation of Akt/protein kinase B in melanoma leads to up-regulation of nuclear factor-kappaB and tumor progression. Cancer Res 62: 7335–7342, 2002

    Google Scholar 

  87. Celebi JT, Shendrik I, Silvers DN, Peacocke M: Identification of PTEN mutations in metastatic melanoma specimens. J Med Genet 37: 653–657, 2000

    Google Scholar 

  88. Zhou XP, Gimm O, Hampel H, Niemann T, Walker MJ, Eng C: Epigenetic PTEN silencing in malignant melanomas without PTEN mutation. Am J Pathol 157: 1123–1128, 2000

    Google Scholar 

  89. Tsao H, Mihm MC, Jr., Sheehan C: PTEN expression in normal skin, acquired melanocytic nevi, and cutaneous melanoma. J Am Acad Dermatol 49: 865–872, 2003

    Google Scholar 

  90. Mayo MW, Wang CY, Cogswell PC, Rogers-Graham KS, Lowe SW, Der CJ, Baldwin AS, Jr.: Requirement of NF-kappaB activation to suppress p53-independent apoptosis induced by oncogenic Ras. Science 278: 1812–1815, 1997

    Google Scholar 

  91. Finco TS, Westwick JK, Norris JL, Beg AA, Der CJ, Baldwin AS, Jr.: Oncogenic Ha-Ras-induced signaling activates NF-kappaB transcriptional activity, which is required for cellular transformation. J Biol Chem 272: 24113–24116, 1997

    Google Scholar 

  92. Norris JL, Baldwin AS, Jr.: Oncogenic Ras enhances NF-kappaB transcriptional activity through Raf-dependent and Raf-independent mitogen-activated protein kinase signaling pathways. J Biol Chem 274: 13841–13846, 1999

    Google Scholar 

  93. Millan O, Ballester A, Castrillo A, Oliva JL, Traves PG, Rojas JM, Bosca L: H-Ras-specific activation of NF-kappaB protects NIH 3T3 cells against stimulus-dependent apoptosis. Oncogene 22: 477–483, 2003

    Google Scholar 

  94. Herlyn M, Satyamoorthy K: Activated ras. Yet another player in melanoma? Am J Pathol 149: 739–744, 1996

    Google Scholar 

  95. Castellano M, Parmiani G: Genes involved in melanoma: An overview of INK4a and other loci. Melanoma Res 9: 421–432, 1999

    Google Scholar 

  96. Pollock PM, Harper UL, Hansen KS, Yudt LM, Stark M, Robbins CM, Moses TY, Hostetter G, Wagner U, Kakareka J, Salem G, Pohida T, Heenan P, Duray P, Kallioniemi O, Hayward NK, Trent JM, Meltzer PS: High frequency of BRAF mutations in nevi. Nat Genet 33: 19–20, 2003

    Google Scholar 

  97. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA: Mutations of the BRAF gene in human cancer. Nature 417: 949–954, 2002

    Google Scholar 

  98. Troppmair J, Hartkamp J, Rapp UR: Activation of NF-kappa B by oncogenic Raf in HEK 293 cells occurs through autocrine recruitment of the stress kinase cascade. Oncogene 17: 685–690, 1998

    Google Scholar 

  99. Yin MJ, Christerson LB, Yamamoto Y, Kwak YT, Xu S, Mercurio F, Barbosa M, Cobb MH, Gaynor RB: HTLV-I Tax protein binds to MEKK1 to stimulate IkappaB kinase activity and NF-kappaB activation. Cell 93: 875–884, 1998

    Google Scholar 

  100. Chu ZL, DiDonato JA, Hawiger J, Ballard DW: The tax oncoprotein of human T-cell leukemia virus type 1 associates with and persistently activates IkappaB kinases containing IKKalpha and IKKbeta. J Biol Chem 273: 15891–15894, 1998

    Google Scholar 

  101. Geleziunas R, Ferrell S, Lin X, Mu Y, Cunningham ET, Jr., Grant M, Connelly MA, Hambor JE, Marcu KB, Greene WC: Human T-cell leukemia virus type 1 Tax induction of NF-kappaB involves activation of the IkappaB kinase alpha (IKKalpha) and IKKbeta cellular kinases. Mol Cell Biol 18: 5157–5165, 1998

    Google Scholar 

  102. Mosialos G: The role of Rel/NF-kappa B proteins in viral oncogenesis and the regulation of viral transcription. Semin Cancer Biol 8: 121–129, 1997

    Google Scholar 

  103. La Porta CA, Comolli R: PKC-dependent modulation of IkB alpha-NFkB pathway in low metastatic B16F1 murine melanoma cells and in highly metastatic BL6 cells. Anticancer Res 18: 2591–2597, 1998

    Google Scholar 

  104. Biswas DK, Dai SC, Cruz A, Weiser B, Graner E, Pardee AB: The nuclear factor kappa B (NF-kappa B): A potential therapeutic target for estrogen receptor negative breast cancers. Proc Natl Acad Sci USA 98: 10386–10391, 2001

    Google Scholar 

  105. Wilson L, Szabo C, Salzman AL: Protein kinase C-dependent activation of NF-kappaB in enterocytes is independent of IkappaB degradation. Gastroenterology 117: 106–114, 1999

    Google Scholar 

  106. Han Y, Meng T, Murray NR, Fields AP, Brasier AR: Interleukin-1-induced nuclear factor-kappaB-IkappaBalpha autoregulatory feedback loop in hepatocytes. A role for protein kinase calpha in post-transcriptional regulation of ikappabalpha resynthesis. J Biol Chem 274: 939–947, 1999

    Google Scholar 

  107. Anrather J, Csizmadia V, Soares MP, Winkler H: Regulation of NF-kappaB RelA phosphorylation and transcriptional activity by p21(ras) and protein kinase Czeta in primary endothelial cells. J Biol Chem 274: 13594–13603, 1999

    Google Scholar 

  108. Wang D, Baldwin AS, Jr.: Activation of nuclear factor-kappaB-dependent transcription by tumor necrosis factor-alpha is mediated through phosphorylation of RelA/p65 on serine 529. J Biol Chem 273: 29411–29416, 1998

    Google Scholar 

  109. Wang D, Westerheide SD, Hanson JL, Baldwin AS, Jr.: Tumor necrosis factor alpha-induced phosphorylation of RelA/p65 on Ser529 is controlled by casein kinase II. J Biol Chem 275: 32592–32597, 2000

    Google Scholar 

  110. Sakurai H, Chiba H, Miyoshi H, Sugita T, Toriumi W: IkappaB kinases phosphorylate NF-kappaB p65 subunit on serine 536 in the transactivation domain. J Biol Chem 274: 30353–30356, 1999

    Google Scholar 

  111. Zhong H, SuYang H, Erdjument-Bromage H, Tempst P, Ghosh S: The transcriptional activity of NF-kappaB is regulated by the IkappaB-associated PKAc subunit through a cyclic AMP-independent mechanism. Cell 89: 413–424, 1997

    Google Scholar 

  112. Zhong H, Voll RE, Ghosh S: Phosphorylation of NF-kappa B p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300. Mol Cell 1: 661–671, 1998

    Google Scholar 

  113. Vermeulen L, De Wilde G, Van Damme P, Vanden Berghe W, Haegeman G: Transcriptional activation of the NF-kappaB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1). Embo J 22: 1313–1324, 2003

    Google Scholar 

  114. Berman KS, Verma UN, Harburg G, Minna JD, Cobb MH, Gaynor RB: Sulindac enhances tumor necrosis factor-alpha-mediated apoptosis of lung cancer cell lines by inhibition of nuclear factor-kappaB. Clin Cancer Res 8: 354–360, 2002

    Google Scholar 

  115. May MJ, D’Acquisto F, Madge LA, Glockner J, Pober JS, Ghosh S: Selective inhibition of NF-kappaB activation by a peptide that blocks the interaction of NEMO with the IkappaB kinase complex. Science 289: 1550–1554, 2000

    Google Scholar 

  116. Yamamoto Y, Gaynor RB: Therapeutic potential of inhibition of the NF-kappaB pathway in the treatment of inflammation and cancer. J Clin Invest 107: 135–142, 2001

    Google Scholar 

  117. Hideshima T, Chauhan D, Richardson P, Mitsiades C, Mitsiades N, Hayashi T, Munshi N, Dang L, Castro A, Palombella V, Adams J, Anderson KC: NF-kappa B as a therapeutic target in multiple myeloma. J Biol Chem 277: 16639–16647, 2002

    Google Scholar 

  118. Tan C, Waldmann TA: Proteasome inhibitor PS-341, a potential therapeutic agent for adult T-cell leukemia. Cancer Res 62: 1083–1086, 2002

    Google Scholar 

  119. Adams J: Proteasome inhibition: A novel approach to cancer therapy. Trends Mol Med 8: S49–54, 2002

    Google Scholar 

  120. Amiri KI, Horton LW, LaFleur BJ, Sosman JA, Richmond A: Augmenting chemosensitivity of malignant melanoma tumors via proteasome inhibition: Implication for bortezomib (VELCADE, PS-341) as a therapeutic agent for malignant melanoma. Cancer Res 64: 4912–4918, 2004

    Google Scholar 

  121. Banerji A, Chakrabarti J, Mitra A, Chatterjee A: Effect of curcumin on gelatinase A (MMP-2) activity in B16F10 melanoma cells. Cancer Lett 211: 235–242, 2004

    Google Scholar 

  122. Odot J, Albert P, Carlier A, Tarpin M, Devy J, Madoulet C: In vitro and in vivo anti-tumoral effect of curcumin against melanoma cells. Int J Cancer 111: 381–387, 2004

    Google Scholar 

  123. Chawla-Sarkar M, Bauer JA, Lupica JA, Morrison BH, Tang Z, Oates RK, Almasan A, DiDonato JA, Borden EC, Lindner DJ: Suppression of NF-kappa B survival signaling by nitrosylcobalamin sensitizes neoplasms to the anti-tumor effects of Apo2L/TRAIL. J Biol Chem 278: 39461–39469, 2003

    Google Scholar 

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Authors and Affiliations

  1. Department of Veterans Affairs, Nashville, TN and Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, 37232

    Katayoun I. Amiri & Ann Richmond

  2. Department of Microbiology, Meharry Medical College, Nashville, TN, 37208

    Katayoun I. Amiri & Ann Richmond

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  1. Katayoun I. Amiri
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  2. Ann Richmond
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Correspondence to Ann Richmond.

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Amiri, K.I., Richmond, A. Role of nuclear factor-κ B in melanoma. Cancer Metastasis Rev 24, 301–313 (2005). https://doi.org/10.1007/s10555-005-1579-7

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  • DOI: https://doi.org/10.1007/s10555-005-1579-7

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