Nuclear Factor-κB Activation: From Bench to Bedside

Nuclear factor-κB (NF-κB) is a proinflammatory transcription factor that has emerged as an important player in the development and progression of malignant cancers. NF-κB targets genes that promote tumor cell proliferation, survival, metastasis, inflammation, invasion, and angiogenesis. Constitutive or aberrant activation of NF-κ is frequently encountered in many human tumors and is associated with a resistant phenotype and poor prognosis. The mechanism of such persistent NF-κB activation is not clear but may involve defects in signaling pathways, mutations, or chromosomal rearrangements. Suppression of constitutive NF-κB activation inhibits the oncogenic potential of transformed cells and thus makes NF-κB an interesting new therapeutic target in cancer.

[1]  Y. Ohtsuki,et al.  The establishment of epstein‐barr virus nuclear antigen‐positive (SP‐50B) and epstein‐barr virus nuclear antigen‐negative (SP‐53) cell lines with t(11;14)(q13;q32) chromosome abnormality from an intermediate lymphocytic lymphoma , 1989, Cancer.

[2]  B. Cocks,et al.  A labile repressor acts through the NFkB-like binding sites of the human urokinase gene. , 1991, Nucleic acids research.

[3]  T. Coleman,et al.  Antisense inhibition of the p65 subunit of NF-kappa B blocks tumorigenicity and causes tumor regression. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[4]  J. Johnson,et al.  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. , 1994, The Journal of biological chemistry.

[5]  Tom Maniatis,et al.  The ubiquitinproteasome pathway is required for processing the NF-κB1 precursor protein and the activation of NF-κB , 1994, Cell.

[6]  C. Payá,et al.  LMP-1 activates NF-kappa B by targeting the inhibitory molecule I kappa B alpha , 1995, Journal of virology.

[7]  Kei Yamamoto,et al.  Transcriptional Roles of Nuclear Factor B and Nuclear Factor-Interleukin-6 in the Tumor Necrosis Factor -Dependent Induction of Cyclooxygenase-2 in MC3T3-E1 Cells (*) , 1995, The Journal of Biological Chemistry.

[8]  N. Ueda,et al.  Transcriptional roles of nuclear factor kappa B and nuclear factor-interleukin-6 in the tumor necrosis factor alpha-dependent induction of cyclooxygenase-2 in MC3T3-E1 cells. , 1995, Journal of Biological Chemistry.

[9]  J. Roth,et al.  Altered expression of the p50 subunit of the NF-kappa B transcription factor complex in non-small cell lung carcinoma. , 1995, Oncogene.

[10]  S. Yamaoka,et al.  Constitutive activation of NF‐kappa B is essential for transformation of rat fibroblasts by the human T‐cell leukemia virus type I Tax protein. , 1996, The EMBO journal.

[11]  B. Aggarwal,et al.  Triple helix-forming oligodeoxyribonucleotides targeted to the human tumor necrosis factor (TNF) gene inhibit TNF production and block the TNF-dependent growth of human glioblastoma tumor cells. , 1996, Cancer research.

[12]  S. Ghosh,et al.  Role of unphosphorylated, newly synthesized I kappa B beta in persistent activation of NF-kappa B , 1996, Molecular and cellular biology.

[13]  A. Richmond,et al.  Enhanced Degradation of I-κBα Contributes to Endogenous Activation of NF-κB in Hs294T Melanoma Cells , 1997 .

[14]  A. Richmond,et al.  Enhanced degradation of I-kappaB alpha contributes to endogenous activation of NF-kappaB in Hs294T melanoma cells. , 1997, Cancer research.

[15]  C. Der,et al.  Oncogenic Ha-Ras-induced Signaling Activates NF-κB Transcriptional Activity, Which Is Required for Cellular Transformation* , 1997, The Journal of Biological Chemistry.

[16]  Riaz-ul-Haq,et al.  Activation of nuclear factor-kappaB in cultured endothelial cells by increased glucose concentration: prevention by calphostin C. , 1997, Journal of cardiovascular pharmacology.

[17]  A. E. Rogers,et al.  Aberrant nuclear factor-kappaB/Rel expression and the pathogenesis of breast cancer. , 1997, The Journal of clinical investigation.

[18]  G. Sledge,et al.  Constitutive activation of NF-kappaB during progression of breast cancer to hormone-independent growth , 1997, Molecular and cellular biology.

[19]  B. Dörken,et al.  Constitutive nuclear factor-kappaB-RelA activation is required for proliferation and survival of Hodgkin's disease tumor cells. , 1997, The Journal of clinical investigation.

[20]  M. P. Miano,et al.  Expression of the neoplastic phenotype by human thyroid carcinoma cell lines requires NFκB p65 protein expression , 1997, Oncogene.

[21]  D. Cortez,et al.  A requirement for NF-κB activation in Bcr–Abl-mediated transformation , 1998 .

[22]  B. Aggarwal,et al.  Constitutive activation of NF-kappaB causes resistance to apoptosis in human cutaneous T cell lymphoma HuT-78 cells. Autocrine role of tumor necrosis factor and reactive oxygen intermediates. , 1998, The Journal of biological chemistry.

[23]  M J May,et al.  NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. , 1998, Annual review of immunology.

[24]  D. Cortez,et al.  A requirement for NF-kappaB activation in Bcr-Abl-mediated transformation. , 1998, Genes & development.

[25]  S. Shumway,et al.  Novel IκBα Proteolytic Pathway in WEHI231 Immature B Cells , 1998, Molecular and Cellular Biology.

[26]  R. Hay,et al.  Defective IkappaBalpha in Hodgkin cell lines with constitutively active NF-kappaB. , 1998, Oncogene.

[27]  A. Atfi,et al.  Evidence for a role of NF-kappaB in the survival of hematopoietic cells mediated by interleukin 3 and the oncogenic TEL/platelet-derived growth factor receptor beta fusion protein. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[28]  D. Ballard,et al.  The Tax Oncoprotein of Human T-cell Leukemia Virus Type 1 Associates with and Persistently Activates IκB Kinases Containing IKKα and IKKβ* , 1998, The Journal of Biological Chemistry.

[29]  T. Yoshino,et al.  Establishment and characterization of a mantle cell lymphoma cell line , 1998, British journal of haematology.

[30]  S. Shumway,et al.  Novel IkappaB alpha proteolytic pathway in WEHI231 immature B cells. , 1998, Molecular and cellular biology.

[31]  D. Ballard,et al.  The tax oncoprotein of human T-cell leukemia virus type 1 associates with and persistently activates IkappaB kinases containing IKKalpha and IKKbeta. , 1998, The Journal of biological chemistry.

[32]  P. Thall,et al.  Caspase 2 and caspase 3 protein levels as predictors of survival in acute myelogenous leukemia. , 1998, Blood.

[33]  A. Newby,et al.  Synergistic upregulation of metalloproteinase‐9 by growth factors and inflammatory cytokines: an absolute requirement for transcription factor NF‐κB , 1998, FEBS letters.

[34]  R. Hay,et al.  Defective IκBα in Hodgkin cell lines with constitutively active NF-κB , 1998, Oncogene.

[35]  M. Merville,et al.  Stable inhibition of nuclear factor kappaB in cancer cells does not increase sensitivity to cytotoxic drugs. , 1999, Cancer research.

[36]  C. Der,et al.  Dependence of Dbl and Dbs Transformation on MEK and NF-κB Activation , 1999, Molecular and Cellular Biology.

[37]  J. Romashkova,et al.  NF-κB is a target of AKT in anti-apoptotic PDGF signalling , 1999, Nature.

[38]  A. Richmond,et al.  Elevated Constitutive IκB Kinase Activity and IκB-α Phosphorylation in Hs294T Melanoma Cells Lead to Increased Basal MGSA/GRO-α Transcription , 1999 .

[39]  T. Slaga,et al.  Increased expression of p50-NF-kappaB and constitutive activation of NF-kappaB transcription factors during mouse skin carcinogenesis. , 1999, Oncogene.

[40]  T. Slaga,et al.  Increased expression of p50-NF-κB and constitutive activation of NF-κB transcription factors during mouse skin carcinogenesis , 1999, Oncogene.

[41]  C. Der,et al.  Dependence of Dbl and Dbs transformation on MEK and NF-kappaB activation. , 1999, Molecular and cellular biology.

[42]  C. Van Waes,et al.  Constitutive activation of transcription factors NF‐κB, AP‐1, and NF‐IL6 in human head and neck squamous cell carcinoma cell lines that express pro‐inflammatory and pro‐angiogenic cytokines , 1999, Molecular carcinogenesis.

[43]  W. McBride,et al.  Inhibition of NF-κB, Clonogenicity, and Radiosensitivity of Human Cancer Cells , 1999 .

[44]  Douglas B. Evans,et al.  Overexpression of urokinase-type plasminogen activator in pancreatic adenocarcinoma is regulated by constitutively activated RelA , 1999, Oncogene.

[45]  M. Hayn,et al.  4-Hydroxynonenal prevents NF-kappaB activation and tumor necrosis factor expression by inhibiting IkappaB phosphorylation and subsequent proteolysis. , 1999, The Journal of biological chemistry.

[46]  W. McBride,et al.  Inhibition of NF-kappaB, clonogenicity, and radiosensitivity of human cancer cells. , 1999, Journal of the National Cancer Institute.

[47]  M. Merville,et al.  Regulation of NF-kappaB activity by I kappaB-related proteins in adenocarcinoma cells. , 1999, Oncogene.

[48]  B. Dörken,et al.  Molecular mechanisms of constitutive NF-κB/Rel activation in Hodgkin/Reed-Sternberg cells , 1999, Oncogene.

[49]  Douglas B. Evans,et al.  The Nuclear Factor-κB RelA Transcription Factor Is Constitutively Activated in Human Pancreatic Adenocarcinoma Cells , 1999 .

[50]  D. Wang,et al.  Elevated constitutive IkappaB kinase activity and IkappaB-alpha phosphorylation in Hs294T melanoma cells lead to increased basal MGSA/GRO-alpha transcription. , 1999, Cancer research.

[51]  C. N. Coleman,et al.  Constitutive activation of IκB kinase α and NF-κB in prostate cancer cells is inhibited by ibuprofen , 1999, Oncogene.

[52]  C. N. Coleman,et al.  Constitutive activation of IkappaB kinase alpha and NF-kappaB in prostate cancer cells is inhibited by ibuprofen. , 1999, Oncogene.

[53]  M. Hayn,et al.  4-Hydroxynonenal Prevents NF-κB Activation and Tumor Necrosis Factor Expression by Inhibiting IκB Phosphorylation and Subsequent Proteolysis* , 1999, The Journal of Biological Chemistry.

[54]  J. Abbruzzese,et al.  The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[55]  J. Romashkova,et al.  NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling. , 1999, Nature.

[56]  E. Estey,et al.  Phenylarsine oxide blocks interleukin-1beta-induced activation of the nuclear transcription factor NF-kappaB, inhibits proliferation, and induces apoptosis of acute myelogenous leukemia cells. , 1999, Blood.

[57]  C. Scheidereit,et al.  Transcription factor NF-κB is constitutively activated in acute lymphoblastic leukemia cells , 2000, Leukemia.

[58]  W C Greene,et al.  NF-κB Signaling Promotes Both Cell Survival and Neurite Process Formation in Nerve Growth Factor-Stimulated PC12 Cells , 2000, The Journal of Neuroscience.

[59]  Y. Liaw,et al.  Constitutive activation of nuclear factor κB in hepatocellular carcinoma , 2000 .

[60]  G. Sledge,et al.  Paclitaxel sensitivity of breast cancer cells with constitutively active NF-kappaB is enhanced by IkappaBalpha super-repressor and parthenolide. , 2000, Oncogene.

[61]  W. Funkhouser,et al.  Selective activation of NF-kappa B subunits in human breast cancer: potential roles for NF-kappa B2/p52 and for Bcl-3. , 2000, Oncogene.

[62]  J. Cusack,et al.  Inducible chemoresistance to 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothe cin (CPT-11) in colorectal cancer cells and a xenograft model is overcome by inhibition of nuclear factor-kappaB activation. , 2000, Cancer research.

[63]  A. Pardee,et al.  Epidermal growth factor-induced nuclear factor kappa B activation: A major pathway of cell-cycle progression in estrogen-receptor negative breast cancer cells. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[64]  M. Hung,et al.  HER-2/neu Blocks Tumor Necrosis Factor-induced Apoptosis via the Akt/NF-κB Pathway* , 2000, The Journal of Biological Chemistry.

[65]  S. Ghosh,et al.  Selective inhibition of NF-κB activation by a peptide that blocks the interaction of NEMO with the IκB kinase complex , 2000 .

[66]  Y. Liaw,et al.  Constitutive activation of nuclear factor kappaB in hepatocellular carcinoma. , 2000, Cancer.

[67]  Debajit K. Biswas,et al.  Epidermal growth factor-induced nuclear factor κB activation: A major pathway of cell-cycle progression in estrogen-receptor negative breast cancer cells , 2000 .

[68]  G. Sledge,et al.  Paclitaxel sensitivity of breast cancer cells with constitutively active NF-κB is enhanced by IκBα super-repressor and parthenolide , 2000, Oncogene.

[69]  T. Wirth,et al.  Raf induces NF-kappaB by membrane shuttle kinase MEKK1, a signaling pathway critical for transformation. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[70]  James B. Mitchell,et al.  Cisplatin and radiation sensitivity in human head and neck squamous carcinomas are independently modulated by glutathione and transcription factor NF‐κB , 2000, Head & neck.

[71]  S. Miyamoto,et al.  A switch in distinct I kappa B alpha degradation mechanisms mediates constitutive NF-kappa B activation in mature B cells. , 2000, Journal of immunology.

[72]  E. Kieff,et al.  NF-kappa B inhibition causes spontaneous apoptosis in Epstein-Barr virus-transformed lymphoblastoid cells. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[73]  S. Miyamoto,et al.  A Switch in Distinct IκBα Degradation Mechanisms Mediates Constitutive NF-κB Activation in Mature B Cells1 , 2000, The Journal of Immunology.

[74]  C. Bucana,et al.  Level of interleukin-8 expression by metastatic human melanoma cells directly correlates with constitutive NF-kappaB activity. , 2000, Cytokines, cellular & molecular therapy.

[75]  W. Funkhouser,et al.  Selective activation of NF-κB subunits in human breast cancer: potential roles for NF-κB2/p52 and for Bcl-3 , 2000, Oncogene.

[76]  M. Seppänen,et al.  Activation of transcription factor NF-kappaB by growth inhibitory cytokines in vulvar carcinoma cells. , 2000, Immunology letters.

[77]  J. Pober,et al.  Selective inhibition of NF-kappaB activation by a peptide that blocks the interaction of NEMO with the IkappaB kinase complex. , 2000, Science.

[78]  M. Brännström,et al.  Upregulation of interleukin‐8 and polarized epithelial expression of interleukin‐8 receptor A in ovarian carcinomas , 2000, Acta obstetricia et gynecologica Scandinavica.

[79]  E. Harhaj,et al.  Retroviral oncoprotein Tax induces processing of NF-kappaB2/p100 in T cells: evidence for the involvement of IKKalpha. , 2001, The EMBO journal.

[80]  D. S. Lind,et al.  Nuclear factor-κB is upregulated in colorectal cancer , 2001 .

[81]  J. Diao,et al.  X protein of hepatitis B virus modulates cytokine and growth factor related signal transduction pathways during the course of viral infections and hepatocarcinogenesis. , 2001, Cytokine & growth factor reviews.

[82]  R. Coffey,et al.  Her-2/neu overexpression induces NF-kappaB via a PI3-kinase/Akt pathway involving calpain-mediated degradation of IkappaB-alpha that can be inhibited by the tumor suppressor PTEN. , 2001, Oncogene.

[83]  A. Richmond,et al.  Constitutive IkappaB kinase activity correlates with nuclear factor-kappaB activation in human melanoma cells. , 2001, Cancer research.

[84]  J. Clohisy,et al.  TAT Fusion Proteins Containing Tyrosine 42-deleted IκBα Arrest Osteoclastogenesis* , 2001, The Journal of Biological Chemistry.

[85]  H. Nakayama,et al.  High expression levels of nuclear factor κB, IκB kinase α and Akt kinase in squamous cell carcinoma of the oral cavity , 2001 .

[86]  R. Schmid,et al.  Nuclear factor-kappaB is constitutively active in C-cell carcinoma and required for RET-induced transformation. , 2001, Cancer research.

[87]  T. Bando,et al.  Enhanced IkappaB kinase activity is responsible for the augmented activity of NF-kappaB in human head and neck carcinoma cells. , 2001, Cancer letters.

[88]  Ulrich Siebenlist,et al.  Constitutive Nuclear Factor κB Activity Is Required for Survival of Activated B Cell–like Diffuse Large B Cell Lymphoma Cells , 2001, The Journal of experimental medicine.

[89]  O. Bernard,et al.  Involvement of the NF‐κB pathway in the transforming properties of the TEL–Jak2 leukemogenic fusion protein , 2001, FEBS letters.

[90]  R. Coffey,et al.  Her-2/neu overexpression induces NF-κB via a PI3-kinase/Akt pathway involving calpain-mediated degradation of IκB-α that can be inhibited by the tumor suppressor PTEN , 2001, Oncogene.

[91]  W. Greene,et al.  Duration of nuclear NF-kappaB action regulated by reversible acetylation. , 2001, Science.

[92]  D. Seldin,et al.  Roles of IKK kinases and protein kinase CK2 in activation of nuclear factor-kappaB in breast cancer. , 2001, Cancer research.

[93]  H. Nakayama,et al.  High expression levels of nuclear factor kappaB, IkappaB kinase alpha and Akt kinase in squamous cell carcinoma of the oral cavity. , 2001, Cancer.

[94]  D. S. Lind,et al.  Nuclear factor-kappa B is upregulated in colorectal cancer. , 2001, Surgery.

[95]  N. Mukaida,et al.  Nuclear factor-kappaB-dependent expression of metastasis suppressor KAI1/CD82 gene in lung cancer cell lines expressing mutant p53. , 2001, Cancer research.

[96]  K. Jeang.  Functional activities of the human T-cell leukemia virus type I Tax oncoprotein: cellular signaling through NF-kappa B. , 2001, Cytokine & growth factor reviews.

[97]  M. Tsuneyoshi,et al.  Nuclear factor-kappaB p65 (RelA) transcription factor is constitutively activated in human gastric carcinoma tissue. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[98]  G. Dong,et al.  IL (Interleukin)-1α Promotes Nuclear Factor-κB and AP-1-induced IL-8 Expression, Cell Survival, and Proliferation in Head and Neck Squamous Cell Carcinomas , 2001 .

[99]  C. Van Waes,et al.  IL (interleukin)-1alpha promotes nuclear factor-kappaB and AP-1-induced IL-8 expression, cell survival, and proliferation in head and neck squamous cell carcinomas. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[100]  D. Howard,et al.  Nuclear factor-kappaB is constitutively activated in primitive human acute myelogenous leukemia cells. , 2001, Blood.

[101]  Jingqing Yang,et al.  Constitutive IκB Kinase Activity Correlates with Nuclear Factor-κB Activation in Human Melanoma Cells , 2001 .

[102]  T. Bando,et al.  Enhanced IκB kinase activity is responsible for the augmented activity of NF-κB in human head and neck carcinoma cells , 2001 .

[103]  Masafumi Ohtsubo,et al.  Constitutive activation of nuclear factor-κB prevents TRAIL-induced apoptosis in renal cancer cells , 2001, Oncogene.

[104]  C. Bucana,et al.  Blockade of NF-κB activity in human prostate cancer cells is associated with suppression of angiogenesis, invasion, and metastasis , 2001, Oncogene.

[105]  M. Reitz,et al.  Activation of NF-κB by the Human Herpesvirus 8 Chemokine Receptor ORF74: Evidence for a Paracrine Model of Kaposi's Sarcoma Pathogenesis , 2001, Journal of Virology.

[106]  S. Westerheide,et al.  The Putative Oncoprotein Bcl-3 Induces Cyclin D1 To Stimulate G1 Transition , 2001, Molecular and Cellular Biology.

[107]  E. Harhaj,et al.  Retroviral oncoprotein Tax induces processing of NF‐κB2/p100 in T cells: evidence for the involvement of IKKα , 2001 .

[108]  L. Marnett,et al.  IκB Kinase, a Molecular Target for Inhibition by 4-Hydroxy-2-nonenal* , 2001, The Journal of Biological Chemistry.

[109]  L. Marnett,et al.  IkappaB kinase, a molecular target for inhibition by 4-hydroxy-2-nonenal. , 2001, The Journal of biological chemistry.

[110]  Eric Verdin,et al.  Duration of Nuclear NF-κB Action Regulated by Reversible Acetylation , 2001, Science.

[111]  C. Bucana,et al.  Blockade of NF-kappaB activity in human prostate cancer cells is associated with suppression of angiogenesis, invasion, and metastasis. , 2001, Oncogene.

[112]  R. Ratan,et al.  The Epidermal Growth Factor Receptor Engages Receptor Interacting Protein and Nuclear Factor-κB (NF-κB)-inducing Kinase to Activate NF-κB , 2001, The Journal of Biological Chemistry.

[113]  A. Pardee,et al.  The nuclear factor kappa B (NF-kappa B): a potential therapeutic target for estrogen receptor negative breast cancers. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[114]  R. Ratan,et al.  The epidermal growth factor receptor engages receptor interacting protein and nuclear factor-kappa B (NF-kappa B)-inducing kinase to activate NF-kappa B. Identification of a novel receptor-tyrosine kinase signalosome. , 2001, The Journal of biological chemistry.

[115]  A. Pardee,et al.  The nuclear factor kappa B (NF-κB): A potential therapeutic target for estrogen receptor negative breast cancers , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[116]  Bharat B. Aggarwal,et al.  Nuclear Factor-κB Activation: A Question of Life or Death , 2002 .

[117]  W. Zong,et al.  Mechanisms of constitutive NF‐κB activation in human prostate cancer cells , 2002, The Prostate.

[118]  Sanjeev Banerjee,et al.  Curcumin-induced suppression of cell proliferation correlates with down-regulation of cyclin D1 expression and CDK4-mediated retinoblastoma protein phosphorylation , 2002, Oncogene.

[119]  T. McDonnell,et al.  Establishment and characterization of a new mantle cell lymphoma cell line, Mino. , 2002, Leukemia research.

[120]  Shishir Shishodia,et al.  Nuclear factor-kappaB activation: a question of life or death. , 2002, Journal of biochemistry and molecular biology.

[121]  R. Surabhi,et al.  RNA Interference Directed against Viral and Cellular Targets Inhibits Human Immunodeficiency Virus Type 1 Replication , 2002, Journal of Virology.

[122]  H. Nakshatri,et al.  Identification of signal transduction pathways involved in constitutive NF-κB activation in breast cancer cells , 2002, Oncogene.

[123]  A. Gazdar,et al.  Role of MRIT/cFLIP in Protection Against Chemotherapy-Induced Apoptosis , 2002, Cancer biology & therapy.

[124]  A Garg,et al.  Nuclear transcription factor-κB as a target for cancer drug development , 2002, Leukemia.

[125]  B. Aggarwal,et al.  Nuclear transcription factor-kappaB as a target for cancer drug development. , 2002, Leukemia.

[126]  T. Slaga,et al.  The role of IKK in constitutive activation of NF-kappaB transcription factor in prostate carcinoma cells. , 2002, Journal of cell science.

[127]  G. Chen,et al.  The nuclear localization of NFkappaB and p53 is positively correlated with HPV16 E7 level in laryngeal squamous cell carcinoma. , 2003, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[128]  Sujay K. Singh,et al.  Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and IkappaBalpha kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. , 2003, Blood.

[129]  F. Schmitz,et al.  Increased Expression of RelA/Nuclear Factor-κB Protein Correlates with Colorectal Tumorigenesis , 2003, Oncology.

[130]  N. Sato,et al.  Survivin acts as an antiapoptotic factor during the development of mouse preimplantation embryos. , 2003, Developmental biology.

[131]  D. Karunagaran,et al.  NF-κB is constitutively activated in high-grade squamous intraepithelial lesions and squamous cell carcinomas of the human uterine cervix , 2003, Oncogene.

[132]  R. Surabhi,et al.  TAK1 is Critical for IκB Kinase-mediated Activation of the NF-κB Pathway , 2003 .

[133]  M. R. Hellmich,et al.  Bombesin stimulates nuclear factor kappa B activation and expression of proangiogenic factors in prostate cancer cells. , 2003, Cancer research.

[134]  Masafumi Ohtsubo,et al.  Increased nuclear factor-kappa B activation is related to the tumor development of renal cell carcinoma. , 2003, Carcinogenesis.

[135]  A. Karsan,et al.  Bacterial lipopolysaccharide directly induces angiogenesis through TRAF6-mediated activation of NF-kappaB and c-Jun N-terminal kinase. , 2003, Blood.

[136]  W. Greene,et al.  Regulation of distinct biological activities of the NF-κB transcription factor complex by acetylation , 2003, Journal of Molecular Medicine.

[137]  Channing J Der,et al.  The dark side of Ras: regulation of apoptosis , 2003, Oncogene.

[138]  G. Chen,et al.  The Nuclear Localization of NFκB and p53 Is Positively Correlated with HPV16 E7 Level in Laryngeal Squamous Cell Carcinoma1 , 2003 .

[139]  F. Schmitz,et al.  Increased expression of RelA/nuclear factor-kappa B protein correlates with colorectal tumorigenesis. , 2003, Oncology.

[140]  Sujay K. Singh,et al.  Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor–κB and IκBα kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis , 2003 .

[141]  Douglas B. Evans,et al.  Function of nuclear factor kappaB in pancreatic cancer metastasis. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[142]  Douglas B. Evans,et al.  Function of Nuclear Factor κB in Pancreatic Cancer Metastasis , 2003 .

[143]  B. Salh,et al.  5,6-Dichloro-ribifuranosylbenzimidazole- and apigenin-induced sensitization of colon cancer cells to TNF-alpha-mediated apoptosis. , 2003, American journal of physiology. Gastrointestinal and liver physiology.

[144]  S. Howell,et al.  KSHV vFLIP binds to IKK-gamma to activate IKK. , 2003, Journal of cell science.

[145]  Z. Estrov,et al.  Resveratrol blocks interleukin-1beta-induced activation of the nuclear transcription factor NF-kappaB, inhibits proliferation, causes S-phase arrest, and induces apoptosis of acute myeloid leukemia cells. , 2003, Blood.

[146]  S. Howell,et al.  KSHV vFLIP binds to IKK-γ to activate IKK , 2003, Journal of Cell Science.

[147]  R. Surabhi,et al.  TAK1 is critical for IkappaB kinase-mediated activation of the NF-kappaB pathway. , 2003, Journal of molecular biology.

[148]  H. Nakshatri,et al.  NF-κ B Promotes Breast Cancer Cell Migration and Metastasis by Inducing the Expression of the Chemokine Receptor CXCR4* , 2003, Journal of Biological Chemistry.

[149]  L. Pham,et al.  Inhibition of Constitutive NF-κB Activation in Mantle Cell Lymphoma B Cells Leads to Induction of Cell Cycle Arrest and Apoptosis1 , 2003, The Journal of Immunology.

[150]  F. Giancotti,et al.  Integrin beta4 signaling promotes tumor angiogenesis. , 2004, Cancer cell.

[151]  B. Aggarwal,et al.  Role of chemopreventive agents in cancer therapy. , 2004, Cancer letters.

[152]  W. Wang,et al.  Expression of NF-κB and human telomerase reverse transcriptase in gastric cancer and precancerous lesions , 2004 .

[153]  E. Vellenga,et al.  Constitutive NF-κB DNA-binding activity in AML is frequently mediated by a Ras/PI3-K/PKB-dependent pathway , 2004, Leukemia.

[154]  T. Joh,et al.  Transglutaminase 2 induces NF-κB activation via a novel pathway in BV-2 microglia , 2004 .

[155]  W. Wang,et al.  Expression of NF-kappaB and human telomerase reverse transcriptase in gastric cancer and precancerous lesions. , 2004, World journal of gastroenterology.

[156]  F. Giancotti,et al.  Integrin β4 signaling promotes tumor angiogenesis , 2004 .

[157]  B. Aggarwal,et al.  Nuclear factor-kappaB: the enemy within. , 2004, Cancer cell.

[158]  B. Aggarwal,et al.  Nuclear factor-kappaB activation mediates cellular transformation, proliferation, invasion angiogenesis and metastasis of cancer. , 2004, Cancer treatment and research.

[159]  Terry L. Smith,et al.  Expression of constitutively active nuclear-kappa B RelA transcription factor in blasts of acute myeloid leukemia. , 2004, Human pathology.

[160]  J. Reynolds,et al.  NF-&kgr;B Activation in Esophageal Adenocarcinoma: Relationship to Barrett's Metaplasia, Survival, and Response to Neoadjuvant Chemoradiotherapy , 2004, Annals of surgery.

[161]  Z. Estrov,et al.  Nuclear factor–κB and STAT3 are constitutively active in CD138+ cells derived from multiple myeloma patients, and suppression of these transcription factors leads to apoptosis , 2004 .

[162]  B. Aggarwal,et al.  Nuclear factor‐κB and IκB kinase are constitutively active in human pancreatic cells, and their down‐regulation by curcumin (diferuloylmethane) is associated with the suppression of proliferation and the induction of apoptosis , 2004, Cancer.

[163]  Masao Tanaka,et al.  Increased nuclear factor-kB activation in human colorectal carcinoma and its correlation with tumor progression. , 2004, Anticancer research.

[164]  D. Siegel,et al.  Regulation of NF-kB in multiple myeloma: therapeutic implications. , 2004, Clinical advances in hematology & oncology : H&O.

[165]  E. Rosen,et al.  Role of NF-κB signaling in hepatocyte growth factor/scatter factor-mediated cell protection , 2005, Oncogene.

[166]  M. Resnick,et al.  Constitutive activation of PI3K‐Akt and NF‐κB during prostate cancer progression in autochthonous transgenic mouse model , 2005, The Prostate.

[167]  H. Stein,et al.  Elevated NF-kappaB p50 complex formation and Bcl-3 expression in classical Hodgkin, anaplastic large-cell, and other peripheral T-cell lymphomas. , 2005, Blood.

[168]  H. Lee,et al.  Nuclear Factor-κB Activation Correlates with Better Prognosis and Akt Activation in Human Gastric Cancer , 2005, Clinical Cancer Research.

[169]  G. Kroemer,et al.  NF-κB constitutes a potential therapeutic target in high-risk myelodysplastic syndrome , 2005 .

[170]  P. Rath.  Relationship between constitutive nuclear factor-kappaB (NF-κB) and inhibitor kappaB-alpha (IκB-α) in an interferon-α-sensitive human Burkitt lymphoma cell line , 2005 .

[171]  L. Staudt,et al.  MALT1 and the API2-MALT1 fusion act between CD40 and IKK and confer NF-kappa B-dependent proliferative advantage and resistance against FAS-induced cell death in B cells. , 2005, Blood.

[172]  Luc Y. Dirix,et al.  Distinct Molecular Signature of Inflammatory Breast Cancer by cDNA Microarray Analysis , 2005, Breast Cancer Research and Treatment.

[173]  B. Aggarwal,et al.  Transcription Factor NF‐κB: A Sensor for Smoke and Stress Signals , 2005 .

[174]  P. Rath.  Relationship between constitutive nuclear factor-kappaB (NF-kappaB) and inhibitor kappaB-alpha (IkappaB-alpha) in an interferon-alpha-sensitive human Burkitt lymphoma cell line. , 2005, Biochimica et biophysica acta.

[175]  B. Aggarwal,et al.  Transcription factor NF-kappaB: a sensor for smoke and stress signals. , 2005, Annals of the New York Academy of Sciences.

[176]  A. Garg,et al.  Chemosensitization and radiosensitization of tumors by plant polyphenols. , 2005, Antioxidants & redox signaling.

[177]  G. Hortobagyi,et al.  The nuclear transcription factor kappaB/bcl-2 pathway correlates with pathologic complete response to doxorubicin-based neoadjuvant chemotherapy in human breast cancer. , 2005, Clinical cancer research : an official journal of the American Association for Cancer Research.

[178]  H. Stein,et al.  Elevated NF-κB p50 complex formation and Bcl-3 expression in classical Hodgkin, anaplastic large-cell, and other peripheral T-cell lymphomas , 2005 .

[179]  C. Le Page,et al.  EGFR and Her‐2 regulate the constitutive activation of NF‐kappaB in PC‐3 prostate cancer cells , 2005, The Prostate.

[180]  H. Lee,et al.  Nuclear factor-kappaB activation correlates with better prognosis and Akt activation in human gastric cancer. , 2005, Clinical cancer research : an official journal of the American Association for Cancer Research.

[181]  B. Aggarwal,et al.  Curcumin (diferuloylmethane) inhibits constitutive NF-kappaB activation, induces G1/S arrest, suppresses proliferation, and induces apoptosis in mantle cell lymphoma. , 2005, Biochemical pharmacology.

[182]  M. Resnick,et al.  Constitutive activation of P I3 K-Akt and NF-kappaB during prostate cancer progression in autochthonous transgenic mouse model. , 2005, The Prostate.

[183]  J. Ajani,et al.  Association of activated transcription factor nuclear factor kappab with chemoradiation resistance and poor outcome in esophageal carcinoma. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[184]  Diane D. Liu,et al.  Nuclear factor-kappaB (NF-kappaB) is frequently expressed in lung cancer and preneoplastic lesions. , 2006, Cancer.

[185]  B. Aggarwal,et al.  Inflammation and cancer: how hot is the link? , 2006, Biochemical pharmacology.

[186]  P. Dent,et al.  Constitutive activation of NF-kappaB in human hepatocellular carcinoma: evidence of a cytoprotective role. , 2006, Human gene therapy.

[187]  Y. Oshika,et al.  P-glycoprotein-mediated acquired multidrug resistance of human lung cancer cells in vivo. , 1996, British Journal of Cancer.

[188]  G. Kroemer,et al.  NF-kappaB constitutes a potential therapeutic target in high-risk myelodysplastic syndrome. , 2006, Blood.

[189]  Shishir Shishodia,et al.  Molecular targets of dietary agents for prevention and therapy of cancer. , 2006, Biochemical pharmacology.

[190]  Michael Karin,et al.  Regulation and Function of IKK and IKK-Related Kinases , 2006, Science's STKE.

[191]  Bharat B. Aggarwal,et al.  Nuclear factor‐κB (nf‐κB) is frequently expressed in lung cancer and preneoplastic lesions , 2006 .

[192]  Overexpression of tissue transglutaminase leads to constitutive activation of nuclear factor-kappaB in cancer cells: delineation of a novel pathway. , 2006, Cancer research.

[193]  Hyeyoung Kim.  Oxidative stress in Helicobacter pylori-induced gastric cell injury , 2006, InflammoPharmacology.

[194]  B. Aggarwal,et al.  Role of NF-κB and NF-κB-regulated gene products in chemoresistance and radioresistance , 2006 .

[195]  B. Aggarwal,et al.  Nuclear Factor-κB: A Holy Grail in Cancer Prevention and Therapy , 2006 .

[196]  R. Vobořil,et al.  Constitutive NF-kappaB activity in colorectal cancer cells: impact on radiation-induced NF-kappaB activity, radiosensitivity, and apoptosis. , 2006, Neoplasma.

[197]  B. Aggarwal,et al.  Butein, a tetrahydroxychalcone, inhibits nuclear factor (NF)-kappaB and NF-kappaB-regulated gene expression through direct inhibition of IkappaBalpha kinase beta on cysteine 179 residue. , 2007, The Journal of biological chemistry.

[198]  M. V. Van Dyke,et al.  Constitutive and inducible nuclear factor-kappaB in immortalized normal human bronchial epithelial and non-small cell lung cancer cell lines. , 2007, Cancer letters.

[199]  B. Aggarwal,et al.  Butein, a Tetrahydroxychalcone, Inhibits Nuclear Factor (NF)-κB and NF-κB-regulated Gene Expression through Direct Inhibition of IκBα Kinase β on Cysteine 179 Residue* , 2007, Journal of Biological Chemistry.

[200]  B. Aggarwal,et al.  Evidence that TNF-TNFR1-TRADD-TRAF2-RIP-TAK1-IKK pathway mediates constitutive NF-κB activation and proliferation in human head and neck squamous cell carcinoma , 2007, Oncogene.

[201]  B. Aggarwal,et al.  Epidermal growth factor (EGF) activates nuclear factor-kappaB through IkappaBalpha kinase-independent but EGF receptor-kinase dependent tyrosine 42 phosphorylation of IkappaBalpha. , 2007, Oncogene.

[202]  D. Germain,et al.  Targeting the ubiquitin-proteasome pathway in cancer therapy. , 2007, Anti-cancer agents in medicinal chemistry.

[203]  B. Aggarwal,et al.  Salinosporamide A (NPI-0052) potentiates apoptosis, suppresses osteoclastogenesis, and inhibits invasion through down-modulation of NF-kappaB regulated gene products. , 2007, Blood.