Clinicopathological significance of nuclear factor‐κB activation in hepatocellular carcinoma

Aim:  Nuclear factor‐κB (NF‐κB) is a critical signaling mediator in inflammation, apoptosis resistance and oncogenesis. It has been reported that NF‐κB is activated in several cancers, including hepatocellular carcinoma (HCC). Studies of genetic disruptions in mice also suggest that NF‐κB plays critical roles in hepatocarcinogenesis. The aim of the present study is to characterize NF‐κB activation and correlate it with the degree of malignancy in HCC.

[1]  Y. Morioka,et al.  Postoperative Recurrence of Hepatocellular Carcinoma , 1990, Annals of surgery.

[2]  H. Papadaki,et al.  ILK overexpression in human hepatocellular carcinoma and liver cirrhosis correlates with activation of Akt. , 2008, Oncology reports.

[3]  C. Mendoza-Milla,et al.  NF‐κB activation but not PI3K/Akt is required for dexamethasone dependent protection against TNF‐α cytotoxicity in L929 cells , 2005 .

[4]  Xianglin Shi,et al.  New Insights into the Role of Nuclear Factor-κB in Cell Growth Regulation , 2001 .

[5]  D. Seldin,et al.  Protein kinase CK2 promotes aberrant activation of nuclear factor-kappaB, transformed phenotype, and survival of breast cancer cells. , 2002, Cancer research.

[6]  Noriyuki Moriyama,et al.  Pathology of small hepatocellular carcinoma. A proposal for a new gross classification , 1987, Cancer.

[7]  Mark Manfredi,et al.  MLN4924, a NEDD8-activating enzyme inhibitor, is active in diffuse large B-cell lymphoma models: rationale for treatment of NF-{kappa}B-dependent lymphoma. , 2010, Blood.

[8]  A. Hoffmann,et al.  CK2 Is a C-Terminal IκB Kinase Responsible for NF-κB Activation during the UV Response , 2003 .

[9]  M. Karin,et al.  NF-κB signaling, liver disease and hepatoprotective agents , 2008, Oncogene.

[10]  Michael Karin,et al.  IKKβ Couples Hepatocyte Death to Cytokine-Driven Compensatory Proliferation that Promotes Chemical Hepatocarcinogenesis , 2005, Cell.

[11]  Liver Cancer Study Group of Japan.  The general rules for the clinical and pathological study of primary liver cancer , 2006, The Japanese journal of surgery.

[12]  S. Hirohashi,et al.  Akt phosphorylation is a risk factor for early disease recurrence and poor prognosis in hepatocellular carcinoma , 2005, Cancer.

[13]  D. Seldin,et al.  Protein Kinase CK2 Promotes Aberrant Activation of Nuclear Factor-κB, Transformed Phenotype, and Survival of Breast Cancer Cells , 2002 .

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

[15]  Kuen-Feng Chen,et al.  Synergistic interactions between sorafenib and bortezomib in hepatocellular carcinoma involve PP2A-dependent Akt inactivation. , 2010, Journal of hepatology.

[16]  E. Kandel,et al.  The regulation and activities of the multifunctional serine/threonine kinase Akt/PKB. , 1999, Experimental cell research.

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

[18]  A. Hoffmann,et al.  CK2 Is a C-Terminal IkappaB Kinase Responsible for NF-kappaB Activation during the UV Response. , 2003, Molecular cell.

[19]  C. Mendoza-Milla,et al.  NF-kappaB activation but not PI3K/Akt is required for dexamethasone dependent protection against TNF-alpha cytotoxicity in L929 cells. , 2005, FEBS letters.

[20]  S. R. Datta,et al.  Cellular survival: a play in three Akts. , 1999, Genes & development.

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

[22]  S. Hirohashi,et al.  Production of alpha-fetoprotein and normal serum proteins by xenotransplanted human hepatomas in relation to their growth and morphology. , 1979, Cancer research.

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

[24]  J. Ventura,et al.  Dexamethasone protection from TNF-alpha-induced cell death in MCF-7 cells requires NF-kappaB and is independent from AKT , 2006, BMC Cell Biology.

[25]  M. Kurrer,et al.  A lymphotoxin-driven pathway to hepatocellular carcinoma. , 2009, Cancer cell.

[26]  S. Hirohashi,et al.  Cell motility mediated by rho and rho‐associated protein kinase plays a critical role in intrahepatic metastasis of human hepatocellular carcinoma , 1999, Hepatology.

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

[28]  Y. Ben-Neriah,et al.  NF-κB functions as a tumour promoter in inflammation-associated cancer , 2004, Nature.

[29]  David Baltimore,et al.  Inducibility of κ immunoglobulin enhancer-binding protein NF-κB by a posttranslational mechanism , 1986, Cell.

[30]  M. Karin,et al.  Hepatocyte IKKbeta/NF-kappaB inhibits tumor promotion and progression by preventing oxidative stress-driven STAT3 activation. , 2010, Cancer cell.

[31]  J. Testa,et al.  Perturbations of the AKT signaling pathway in human cancer , 2005, Oncogene.

[32]  D. Baltimore,et al.  Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. , 1986, Cell.

[33]  S. Ghosh,et al.  Toll-like receptor-mediated NF-kappaB activation: a phylogenetically conserved paradigm in innate immunity. , 2001, The Journal of clinical investigation.

[34]  Y. Morioka,et al.  Hepatic resection for hepatocellular carcinoma. Clinical features and long-term prognosis. , 1987 .

[35]  K. Shirabe,et al.  Risk factors of the recurrence of hepatocellular carcinoma originating from residual cancer cells after hepatectomy. , 1999, Hepato-gastroenterology.

[36]  Rinat Abramovitch,et al.  NF-kappaB functions as a tumour promoter in inflammation-associated cancer. , 2004, Nature.

[37]  R. Goldberg,et al.  Expression of Nuclear Factor-kappaB Family Proteins in Hepatocellular Carcinomas , 2007, Oncology.

[38]  D. Baltimore,et al.  I kappa B: a specific inhibitor of the NF-kappa B transcription factor. , 1988, Science.

[39]  F. Chen,et al.  New insights into the role of nuclear factor-kappaB in cell growth regulation. , 2001, The American journal of pathology.

[40]  S. Hirohashi,et al.  Critical involvement of the phosphatidylinositol 3-kinase/Akt pathway in anchorage-independent growth and hematogeneous intrahepatic metastasis of liver cancer. , 2002, Cancer research.

[41]  M. Makuuchi,et al.  Predictive value of gross classification of hepatocellular carcinoma on recurrence and survival after hepatectomy. , 2000, Journal of hepatology.