Skip to main content

Advertisement

SpringerLink
Log in

Exploiting Our Knowledge of NF-κB Signaling for the Treatment of Mammary Cancer

  • Published:
Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Nuclear Factor-kappaB (NF-κB) has been implicated in the lobuloalveolar development of the mammary gland. In breast cancer its activation has been linked to tumor progression via stimulation of cell proliferation, pro-survival, and angiogenesis pathways and metastasis. Whether NF-κB activation in the immune system influences mammary cancer remains unclear. In addition to the constitutive activation frequently found in mammary carcinoma tissue, radio- and chemotherapeutic agents used in the treatment of mammary cancer can lead to activation of NF-κB. This effect has been postulated to contribute to the development of resistance to these agents and suggests the use of NF-κB inhibitors as sensitizers for therapy. The review describes principle targets and drugs used to inhibit NF-κB function and discusses future perspectives in the use of these inhibitors for the treatment of mammary cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2

Similar content being viewed by others

Abbreviations

AP-1:

activator protein 1

CAT:

chlor-amphenicol-acetyltransferase

CHIP:

chromatin immunoprecipitation

CK2:

casein kinase 2

COX:

cyclooxygenase

DHMEQ:

dehydroxymethylepoxyquinomicin

DMBA:

7,12-dimethylbenz[a]anthracene

3-Cl-AHPC:

4-[3-Cl-(1-adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic acid

ELISA:

enzyme-linked immunosorbent assay

EMSA:

electrophoretic mobility shift assay

ER:

estrogen receptor

GSK3:

glycogen synthase kinase 3

ICAM:

intercellular adhesion molecule

IGF:

insulin-like growth factor

IGF-IR:

insulin-like growth factors I receptor

IκB:

inhibitor of kappaB

IKK:

IkappaB kinase

IL:

interleukin

MEF:

mouse embryonic fibroblast

MMP:

matrix metalloproteinase

NEMO:

NF-κB essential modulator

NF-κB:

Nuclear Factor-kappaB

NIK:

NF-kappaB-inducing kinase

NK cells:

natural killer cells

NLS:

nuclear localization sequence

NSAID:

non-steroidal anti-inflammatory drugs

PI3-kinase:

Phosphatidylinositol-3-kinase

RANK:

receptor activator of NF-κB

RANKL:

receptor activator of NF-κB ligand

RHD:

Rel homology domain

RT-PCR:

reverse-transcription-polymerase chain reaction

SCID:

severe combined immunodeficiency

STAT:

signal transducer and activator of transcription

TAM:

tumor-associated macrophage

TGF:

transforming growth factor

TNF:

tumor necrosis factor

VCAM:

vascular cell adhesion molecule

VEGF:

vascular endothelial growth factor

References

  1. Ghosh S, May MJ, Kopp EB. NF-kappaB and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol 1998;16:225–60.

    Article  PubMed  CAS  Google Scholar 

  2. Cao Y, Karin M. NF-kappaB in mammary gland development and breast cancer. J Mammary Gland Biol Neoplasia 2003;8:215–23.

    Article  PubMed  Google Scholar 

  3. Luo JL, Kamata H, Karin M. IKK/NF-kappaB signaling: balancing life and death-a new approach to cancer therapy. J Clin Invest 2005;115:2625–32.

    Article  PubMed  CAS  Google Scholar 

  4. Orlowski RZ, Baldwin AS, Jr. NF-kappaB as a therapeutic target in cancer. Trends Mol Med 2002;8:385–9.

    Article  PubMed  CAS  Google Scholar 

  5. Ravi R, Bedi A. NF-kappaB in cancer-a friend turned foe. Drug Resist Updat 2004;7:53–67.

    Article  PubMed  CAS  Google Scholar 

  6. Ghosh S, Karin M. Missing pieces in the NF-kappaB puzzle. Cell 2002;109 Suppl:S81–S96.

    Article  Google Scholar 

  7. Chen LF, Greene WC. Shaping the nuclear action of NF-kappaB. Nat Rev Mol Cell Biol 2004;5:392–401.

    Article  PubMed  CAS  Google Scholar 

  8. Campbell KJ, Rocha S, Perkins ND. Active repression of antiapoptotic gene expression by RelA(p65) NF-kappaB. Mol Cell 2004;13:853–65.

    Article  PubMed  CAS  Google Scholar 

  9. Geymayer S, Doppler W. Activation of NF-kappaB p50/p65 is regulated in the developing mammary gland and inhibits STAT5-mediated beta-casein gene expression. Faseb J 2000;14:1159–70.

    PubMed  CAS  Google Scholar 

  10. Faraldo MM, Deugnier MA, Tlouzeau S, Thiery JP, Glukhova MA. Perturbation of beta1-integrin function in involuting mammary gland results in premature dedifferentiation of secretory epithelial cells. Mol Biol Cell 2002;13:3521–31.

    Article  PubMed  CAS  Google Scholar 

  11. Clarkson RW, Heeley JL, Chapman R, Aillet F, Hay RT, Wyllie A, Watson CJ. NF-kappaB inhibits apoptosis in murine mammary epithelia. J Biol Chem 2000;275:12737–42.

    Article  PubMed  CAS  Google Scholar 

  12. Li Q, Verma IM. NF-kappaB regulation in the immune system. Nat Rev Immunol 2002;2:725–34.

    Article  PubMed  CAS  Google Scholar 

  13. Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 2004;4:71–8.

    Article  PubMed  CAS  Google Scholar 

  14. Kim DW, Sovak MA, Zanieski G, Nonet G, Romieu-Mourez R, Lau AW, Hafer LJ, Yaswen P, Stampfer M, Rogers AE, Russo J, Sonenshein GE. Activation of NF-kappaB/Rel occurs early during neoplastic transformation of mammary cells. Carcinogenesis 2000;21:871–9.

    Article  PubMed  Google Scholar 

  15. Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ, Kagnoff MF, Karin M. IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 2004;118:285–96.

    Article  PubMed  CAS  Google Scholar 

  16. Howe LR, Dannenberg AJ. COX-2 inhibitors for the prevention of breast cancer. J Mammary Gland Biol Neoplasia 2003;8:31–43.

    Article  PubMed  Google Scholar 

  17. Pereg D, Lishner M. Non-steroidal anti-inflammatory drugs for the prevention and treatment of cancer. J Intern Med 2005;258:115–23.

    Article  PubMed  CAS  Google Scholar 

  18. Sporn MB, Suh N. Chemoprevention: an essential approach to controlling cancer. Nat Rev Cancer 2002;2:537–43.

    Article  PubMed  CAS  Google Scholar 

  19. Messina MJ, Loprinzi CL. Soy for breast cancer survivors: a critical review of the literature. J Nutr 2001;131:3095S–108S.

    PubMed  CAS  Google Scholar 

  20. 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 1997;100:2952–60.

    Article  PubMed  CAS  Google Scholar 

  21. 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 1997;17:3629–39.

    PubMed  CAS  Google Scholar 

  22. Cogswell PC, Guttridge DC, Funkhouser WK, Baldwin AS, Jr. Selective activation of NF-kappaB subunits in human breast cancer: potential roles for NF-kappaB2/p52 and for Bcl-3. Oncogene 2000;19:1123–31.

    Article  PubMed  CAS  Google Scholar 

  23. Hou MF, Lin SB, Yuan SS, Tsai SM, Wu SH, Ou-Yang F, Hsieh JS, Tsai KB, Huang TJ, Tsai LY. The clinical significance between activation of nuclear factor kappaB transcription factor and overexpression of HER-2/neu oncoprotein in Taiwanese patients with breast cancer. Clin Chim Acta 2003;334:137–44.

    Article  PubMed  CAS  Google Scholar 

  24. Biswas DK, Shi Q, Baily S, Strickland I, Ghosh S, Pardee AB, Iglehart JD. NF-kappaB activation in human breast cancer specimens and its role in cell proliferation and apoptosis. Proc Natl Acad Sci USA 2004;101:10137–42.

    Article  PubMed  CAS  Google Scholar 

  25. Zhou Y, Eppenberger-Castori S, Marx C, Yau C, Scott GK, Eppenberger U, Benz CC. Activation of nuclear factor-kappaB (NF-kappaB) identifies a high-risk subset of hormone-dependent breast cancers. Int J Biochem Cell Biol 2005;37:1130–44.

    Article  PubMed  CAS  Google Scholar 

  26. Pahl HL. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 1999;18:6853–66.

    Article  PubMed  CAS  Google Scholar 

  27. Zhou BP, Hu MC, Miller SA, Yu Z, Xia W, Lin SY, Hung MC. HER-2/neu blocks tumor necrosis factor-induced apoptosis via the Akt/NF-kappaB pathway. J Biol Chem 2000;275:8027–31.

    Article  PubMed  CAS  Google Scholar 

  28. Biswas DK, Cruz AP, Gansberger E, Pardee AB. Epidermal growth factor-induced nuclear factor kappaB activation: a major pathway of cell-cycle progression in estrogen-receptor negative breast cancer cells. Proc Natl Acad Sci USA 2000;97:8542–7.

    Article  PubMed  CAS  Google Scholar 

  29. Pollak MN, Schernhammer ES, Hankinson SE. Insulin-like growth factors and neoplasia. Nat Rev Cancer 2004;4:505–18.

    Article  PubMed  CAS  Google Scholar 

  30. Clevenger CV, Furth PA, Hankinson SE, Schuler LA. The role of prolactin in mammary carcinoma. Endocr Rev 2003;24:1–27.

    Article  PubMed  CAS  Google Scholar 

  31. Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 2005;5:341–54.

    Article  PubMed  CAS  Google Scholar 

  32. www.clinicaltrials.gov, Identifier: NCT00199212. Accessed January 28, 2006.

  33. Pratt MA, Bishop TE, White D, Yasvinski G, Menard M, Niu MY, Clarke R. Estrogen withdrawal-induced NF-kappaB activity and bcl-3 expression in breast cancer cells: roles in growth and hormone independence. Mol Cell Biol 2003;23:6887–900.

    Article  PubMed  CAS  Google Scholar 

  34. Yamauchi H, Stearns V, Hayes DF. The Role of c-ErbB-2 as a predictive factor in breast cancer. Breast Cancer 2001;8:171–183.

    PubMed  CAS  Google Scholar 

  35. Huber MA, Azoitei N, Baumann B, Grunert S, Sommer A, Pehamberger H, Kraut N, Beug H, Wirth T. NF-kappaB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression. J Clin Invest 2004;114:569–81.

    PubMed  CAS  Google Scholar 

  36. Aggarwal BB, Shishodia S, Takada Y, Banerjee S, Newman RA, Bueso-Ramos CE, Price JE. Curcumin suppresses the paclitaxel-induced nuclear factor-kappaB pathway in breast cancer cells and inhibits lung metastasis of human breast cancer in nude mice. Clin Cancer Res 2005;11:7490–8.

    Article  PubMed  CAS  Google Scholar 

  37. Sweeney CJ, Mehrotra S, Sadaria MR, Kumar S, Shortle NH, Roman Y, Sheridan C, Campbell RA, Murry DJ, Badve S, Nakshatri H. The sesquiterpene lactone parthenolide in combination with docetaxel reduces metastasis and improves survival in a xenograft model of breast cancer. Mol Cancer Ther 2005; 4:1004–12.

    Article  PubMed  CAS  Google Scholar 

  38. Gordon AH, O'Keefe RJ, Schwarz EM, Rosier RN, Puzas JE. Nuclear factor-kappaB-dependent mechanisms in breast cancer cells regulate tumor burden and osteolysis in bone. Cancer Res 2005;65: 3209–17.

    PubMed  CAS  Google Scholar 

  39. Guillen C, Martinez P, de Gortazar AR, Martinez ME, Esbrit P. Both N- and C-terminal domains of parathyroid hormone-related protein increase interleukin-6 by nuclear factor-kappaB activation in osteoblastic cells. J Biol Chem 2002;277:28109–17.

    Article  PubMed  CAS  Google Scholar 

  40. Roodman GD. Mechanisms of bone metastasis. N Engl J Med 2004;350:1655–64.

    Article  PubMed  CAS  Google Scholar 

  41. Pommier Y, Sordet O, Antony S, Hayward RL, Kohn KW. Apoptosis defects and chemotherapy resistance: molecular interaction maps and networks. Oncogene 2004;23:2934–49.

    Article  PubMed  CAS  Google Scholar 

  42. Guo G, Wang T, Gao Q, Tamae D, Wong P, Chen T, Chen WC, Shively JE, Wong JY, Li JJ. Expression of ErbB2 enhances radiation-induced NF-kappaB activation. Oncogene 2004;23:535–45.

    Article  PubMed  CAS  Google Scholar 

  43. Baldwin AS. Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB. J Clin Invest 2001; 107:241–6.

    Article  PubMed  CAS  Google Scholar 

  44. Nakanishi C, Toi M. Nuclear factor-kappaB inhibitors as sensitizers to anticancer drugs. Nat Rev Cancer 2005;5:297–309.

    Article  PubMed  CAS  Google Scholar 

  45. Wang X, Omura S, Szweda LI, Yang Y, Berard J, Seminaro J, Wu J. Rapamycin inhibits proteasome activator expression and proteasome activity. Eur J Immunol 1997;27:2781–6.

    Article  PubMed  CAS  Google Scholar 

  46. Ho WC, Dickson KM, Barker PA. Nuclear factor-kappaB induced by doxorubicin is deficient in phosphorylation and acetylation and represses nuclear factor-kappaB-dependent transcription in cancer cells. Cancer Res 2005;65:4273–81.

    Article  PubMed  CAS  Google Scholar 

  47. Farhana L, Dawson MI, Fontana JA. Apoptosis induction by a novel retinoid-related molecule requires nuclear factor-kappaB activation. Cancer Res 2005;65:4909–17.

    Article  PubMed  CAS  Google Scholar 

  48. Ryan KM, Ernst MK, Rice NR, Vousden KH. Role of NF-kappaB in p53-mediated programmed cell death. Nature 2000;404:892–7.

    Article  PubMed  CAS  Google Scholar 

  49. Ryan KM, O'Prey J, Vousden KH. Loss of nuclear factor-kappaB is tumor promoting but does not substitute for loss of p53. Cancer Res 2004;64:4415–8.

    Article  PubMed  CAS  Google Scholar 

  50. Majumdar S, Aggarwal BB. Methotrexate suppresses NF-kappaB activation through inhibition of IkappaBalpha phosphorylation and degradation. J Immunol 2001;167:2911–20.

    PubMed  CAS  Google Scholar 

  51. Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol 2004;22:329–60.

    Article  PubMed  CAS  Google Scholar 

  52. Ichim CV. Revisiting immunosurveillance and immunostimulation: Implications for cancer immunotherapy. J Transl Med 2005;3:8.

    Article  PubMed  CAS  Google Scholar 

  53. Tas SW, de Jong EC, Hajji N, May MJ, Ghosh S, Vervoordeldonk MJ, Tak PP. Selective inhibition of NF-kappaB in dendritic cells by the NEMO-binding domain peptide blocks maturation and prevents T cell proliferation and polarization. Eur J Immunol 2005;35:1164–74.

    Article  PubMed  CAS  Google Scholar 

  54. Zhou J, Zhang J, Lichtenheld MG, Meadows GG. A role for NF-kappaB activation in perforin expression of NK cells upon IL-2 receptor signaling. J Immunol 2002;169:1319–25.

    PubMed  CAS  Google Scholar 

  55. Ben-Baruch A. Host microenvironment in breast cancer development: inflammatory cells, cytokines and chemokines in breast cancer progression: reciprocal tumor-microenvironment interactions. Breast Cancer Res 2003;5:31–6.

    Article  PubMed  CAS  Google Scholar 

  56. Helbig G, Christopherson KW, 2nd, Bhat-Nakshatri P, Kumar S, Kishimoto H, Miller KD, Broxmeyer HE, Nakshatri H. NF-kappaB promotes breast cancer cell migration and metastasis by inducing the expression of the chemokine receptor CXCR4. J Biol Chem 2003;278:21631–8.

    Article  PubMed  CAS  Google Scholar 

  57. Hagemann T, Wilson J, Kulbe H, Li NF, Leinster DA, Charles K, Klemm F, Pukrop T, Binder C, Balkwill FR. Macrophages induce invasiveness of epithelial cancer cells via NF-kappaB and JNK. J Immunol 2005;175:1197–205.

    PubMed  CAS  Google Scholar 

  58. Biswas SK, Gangi L, Paul S, Schioppa T, Saccani A, Sironi M, Bottazzi B, Doni A, Bronte V, Pasqualini F, Vago L, Nebuloni M, Mantovani A, Sica A. A distinct and unique transcriptional programme expressed by tumor-associated macrophages: defective NF-{kappa}B and enhanced IRF-3/STAT1 activation. Blood 2005.

  59. Guttridge DC, Mayo MW, Madrid LV, Wang CY, Baldwin AS, Jr. NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia. Science 2000;289:2363–6.

    Article  PubMed  CAS  Google Scholar 

  60. Gordon JN, Green SR, Goggin PM. Cancer cachexia. QJM 2005;98:779–88.

    Article  PubMed  CAS  Google Scholar 

  61. Biswas DK, Martin KJ, McAlister C, Cruz AP, Graner E, Dai SC, Pardee AB. Apoptosis caused by chemotherapeutic inhibition of nuclear factor-kappaB activation. Cancer Res 2003;63:290–5.

    PubMed  CAS  Google Scholar 

  62. Gong L, Li Y, Nedeljkovic-Kurepa A, Sarkar FH. Inactivation of NF-kappaB by genistein is mediated via Akt signaling pathway in breast cancer cells. Oncogene 2003;22:4702–9.

    Article  PubMed  CAS  Google Scholar 

  63. Li Y, Ahmed F, Ali S, Philip PA, Kucuk O, Sarkar FH. Inactivation of nuclear factor kappaB by soy isoflavone genistein contributes to increased apoptosis induced by chemotherapeutic agents in human cancer cells. Cancer Res 2005;65:6934–42.

    Article  PubMed  CAS  Google Scholar 

  64. Karin M, Yamamoto Y, Wang QM. The IKK NF-kappaB system: a treasure trove for drug development. Nat Rev Drug Discov 2004;3:17–26.

    Article  PubMed  CAS  Google Scholar 

  65. Mabuchi S, Ohmichi M, Nishio Y, Hayasaka T, Kimura A, Ohta T, Saito M, Kawagoe J, Takahashi K, Yada-Hashimoto N, Sakata M, Motoyama T, Kurachi H, Tasaka K, Murata Y. Inhibition of NF-kappaB increases the efficacy of cisplatin in in vitro and in vivo ovarian cancer models. J Biol Chem 2004;279:23477–85.

    Article  PubMed  CAS  Google Scholar 

  66. Hovstadius P, Larsson R, Jonsson E, Skov T, Kissmeyer AM, Krasilnikoff K, Bergh J, Karlsson MO, Lonnebo A, Ahlgren J. A Phase I study of CHS 828 in patients with solid tumor malignancy. Clin Cancer Res 2002;8:2843–50.

    PubMed  CAS  Google Scholar 

  67. Olsen LS, Hjarnaa PJ, Latini S, Holm PK, Larsson R, Bramm E, Binderup L, Madsen MW. Anticancer agent CHS 828 suppresses nuclear factor-kappaB activity in cancer cells through downregulation of IKK activity. Int J Cancer 2004;111:198–205.

    Article  PubMed  CAS  Google Scholar 

  68. Keifer JA, Guttridge DC, Ashburner BP, Baldwin AS, Jr. Inhibition of NF-kappaB activity by thalidomide through suppression of IkappaB kinase activity. J Biol Chem 2001;276:22382–7.

    Article  PubMed  CAS  Google Scholar 

  69. Eleutherakis-Papaiakovou V, Bamias A, Dimopoulos MA. Thalidomide in cancer medicine. Ann Oncol 2004;15:1151–60.

    Article  PubMed  CAS  Google Scholar 

  70. Colleoni M, Gelber S, Goldhirsch A. Treatment of advanced breast cancer: the good, the bad and the ugly. Ann Oncol 2005;16:1219–21.

    Article  PubMed  CAS  Google Scholar 

  71. Singh S, Aggarwal BB. Activation of transcription factor NF-kappaB is suppressed by curcumin (diferuloylmethane). J Biol Chem 1995;270:24995–5000.

    Article  PubMed  CAS  Google Scholar 

  72. Plummer SM, Holloway KA, Manson MM, Munks RJ, Kaptein A, Farrow S, Howells L. Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-kappaB activation via the NIK/IKK signalling complex. Oncogene 1999;18:6013–20.

    Article  PubMed  CAS  Google Scholar 

  73. Somasundaram S, Edmund NA, Moore DT, Small GW, Shi YY, Orlowski RZ. Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res 2002; 62:3868–75.

    PubMed  CAS  Google Scholar 

  74. Kwok BH, Koh B, Ndubuisi MI, Elofsson M, Crews CM. The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IkappaB kinase. Chem Biol 2001;8:759–66.

    Article  PubMed  CAS  Google Scholar 

  75. Holmes-McNary M, Baldwin AS, Jr. Chemopreventive properties of trans-resveratrol are associated with inhibition of activation of the IkappaB kinase. Cancer Res 2000;60:3477–83.

    PubMed  CAS  Google Scholar 

  76. Adams J. The proteasome: a suitable antineoplastic target. Nat Rev Cancer 2004;4:349–60.

    Article  PubMed  CAS  Google Scholar 

  77. Orlowski RZ, Dees EC. The role of the ubiquitination-proteasome pathway in breast cancer: applying drugs that affect the ubiquitin-proteasome pathway to the therapy of breast cancer. Breast Cancer Res 2003;5:1–7.

    Article  PubMed  CAS  Google Scholar 

  78. Gurova KV, Hill JE, Guo C, Prokvolit A, Burdelya LG, Samoylova E, Khodyakova AV, Ganapathi R, Ganapathi M, Tararova ND, Bosykh D, Lvovskiy D, Webb TR, Stark GR, Gudkov AV. Small molecules that reactivate p53 in renal cell carcinoma reveal a NF-{kappa}B-dependent mechanism of p53 suppression in tumors. Proc Natl Acad Sci USA 2005;102: 17448–53.

    Article  PubMed  CAS  Google Scholar 

  79. Eddy SF, Guo S, Demicco EG, Romieu-Mourez R, Landesman-Bollag E, Seldin DC, Sonenshein GE. Inducible IkappaB kinase/IkappaB kinase epsilon expression is induced by CK2 and promotes aberrant nuclear factor-kappaB activation in breast cancer cells. Cancer Res 2005;65:11375–83.

    Article  PubMed  CAS  Google Scholar 

  80. Battistutta R, Sarno S, De Moliner E, Papinutto E, Zanotti G, Pinna LA. The replacement of ATP by the competitive inhibitor emodin induces conformational modifications in the catalytic site of protein kinase CK2. J Biol Chem 2000;275:29618–22.

    Article  PubMed  CAS  Google Scholar 

  81. Hoeflich KP, Luo J, Rubie EA, Tsao MS, Jin O, Woodgett JR. Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation. Nature 2000;406:86–90.

    Article  PubMed  CAS  Google Scholar 

  82. Ariga A, Namekawa J, Matsumoto N, Inoue J, Umezawa K. Inhibition of tumor necrosis factor-alpha-induced nuclear translocation and activation of NF-kappaB by dehydroxymethylepoxyquinomicin. J Biol Chem 2002;277:24625–30.

    Article  PubMed  CAS  Google Scholar 

  83. Matsumoto G, Namekawa J, Muta M, Nakamura T, Bando H, Tohyama K, Toi M, Umezawa K. Targeting of nuclear factor kappaB Pathways by dehydroxymethylepoxyquinomicin, a novel inhibitor of breast carcinomas: antitumor and antiangiogenic potential in vivo. Clin Cancer Res 2005;11:1287–93.

    PubMed  CAS  Google Scholar 

  84. 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 1999;5:412–7.

    Article  PubMed  CAS  Google Scholar 

  85. Takaesu G, Surabhi RM, Park KJ, Ninomiya-Tsuji J, Matsumoto K, Gaynor RB. TAK1 is critical for IkappaB kinase-mediated activation of the NF-kappaB pathway. J Mol Biol 2003;326:105–15.

    Article  PubMed  CAS  Google Scholar 

  86. Lin YZ, Yao SY, Veach RA, Torgerson TR, Hawiger J. Inhibition of nuclear translocation of transcription factor NF-kappaB by a synthetic peptide containing a cell membrane-permeable motif and nuclear localization sequence. J Biol Chem 1995;270:14255–8.

    Article  PubMed  CAS  Google Scholar 

  87. 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 2000;289:1550–4.

    Article  PubMed  CAS  Google Scholar 

  88. Morishita R, Sugimoto T, Aoki M, Kida I, Tomita N, Moriguchi A, Maeda K, Sawa Y, Kaneda Y, Higaki J, Ogihara T. In vivo transfection of cis element “decoy” against nuclear factor-kappaB binding site prevents myocardial infarction. Nat Med 1997; 3:894–9.

    Article  PubMed  CAS  Google Scholar 

  89. Lessard L, Begin LR, Gleave ME, Mes-Masson AM, Saad F. Nuclear localisation of nuclear factor-kappaB transcription factors in prostate cancer: an immunohistochemical study. Br J Cancer 2005;93:1019–23.

    Article  PubMed  CAS  Google Scholar 

  90. Kaltschmidt C, Kaltschmidt B, Henkel T, Stockinger H, Baeuerle PA. Selective recognition of the activated form of transcription factor NF-kappaB by a monoclonal antibody. Biol Chem Hoppe Seyler 1995;376:9–16.

    PubMed  CAS  Google Scholar 

  91. Nowak DE, Tian B, Brasier AR. Two-step cross-linking method for identification of NF-kappaB gene network by chromatin immunoprecipitation. Biotechniques 2005;39:715–25.

    Article  PubMed  CAS  Google Scholar 

  92. Schmidt-Ullrich R, Memet S, Lilienbaum A, Feuillard J, Raphael M, Israel A. NF-kappaB activity in transgenic mice: developmental regulation and tissue specificity. Development 1996;122:2117–28.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Hartmut Glossmann, Michael Naumann and Andreas Jurgeit for invaluable comments on the manuscript.

Author information

Authors and Affiliations

  1. Division Medical Biochemistry, Biocenter, Innsbruck Medical University, Fritz-Pregl-Str. 3, A-6020, Innsbruck, Austria

    Michael C. Haffner, Chiara Berlato & Wolfgang Doppler

Authors
  1. Michael C. Haffner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chiara Berlato
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wolfgang Doppler
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wolfgang Doppler.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Haffner, M.C., Berlato, C. & Doppler, W. Exploiting Our Knowledge of NF-κB Signaling for the Treatment of Mammary Cancer. J Mammary Gland Biol Neoplasia 11, 63–73 (2006). https://doi.org/10.1007/s10911-006-9013-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10911-006-9013-5

Keywords

Search

Navigation