Activation of nuclear factor kappa B in human neuroblastoma cell lines

J Neurochem. 1994 May;62(5):1716-26. doi: 10.1046/j.1471-4159.1994.62051716.x.


The nuclear factor kappa B (NF-kappa B) is a eukaryotic transcription factor. In B cells and macrophages it is constitutively present in cell nuclei, whereas in many other cell types, NF-kappa B translocates from cytosol to nucleus as a result of transduction by tumor necrosis factor alpha (TNF alpha), phorbol ester, and other polyclonal signals. Using neuroblastoma cell lines as models, we have shown that in neural cells NF-kappa B was present in the cytosol and translocated into nuclei as a result of TNF alpha treatment. The TNF alpha-activated NF-kappa B was transcriptionally functional. NF-kappa B activation by TNF alpha was not correlated with cell differentiation or proliferation. However, reagents such as nerve growth factor (NGF) and the phorbol ester phorbol 12-myristate 13-acetate (PMA), which induce phenotypical differentiation of the SH-SY5Y neuroblastoma cell line, activated NF-kappa B, but only in that particular cell line. In a NGF-responsive rat pheochromocytoma cell line, PC12, PMA activated NF-kappa B, whereas NGF did not. In other neuroblastoma cell lines, such as SK-N-Be(2), the lack of PMA induction of differentiation was correlated with the lack of NF-kappa B activation. We found, moreover, that in SK-N-Be(2) cells protein kinase C (PKC) enzymatic activity was much lower compared with that in a control cell line and that the low PKC enzymatic activity was due to low PKC protein expression. NF-kappa B was not activated by retinoic acid, which induced morphological differentiation of all the neuroblastoma cell lines used in the present study. Thus, NF-kappa B activation was not required for neuroblastoma cell differentiation. Furthermore, the results obtained with TNF alpha proved that NF-kappa B activation was not sufficient for induction of neuroblastoma differentiation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Differentiation / drug effects
  • Cell Line
  • Chloramphenicol O-Acetyltransferase / biosynthesis
  • Chloramphenicol O-Acetyltransferase / metabolism
  • Humans
  • Molecular Sequence Data
  • NF-kappa B / metabolism*
  • Nerve Growth Factors / pharmacology
  • Neuroblastoma / metabolism*
  • Nuclear Proteins / isolation & purification
  • Nuclear Proteins / metabolism
  • Oligodeoxyribonucleotides
  • PC12 Cells
  • Protein Kinase C / metabolism
  • Recombinant Proteins / pharmacology
  • T-Lymphocytes
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription, Genetic* / drug effects
  • Transfection
  • Tretinoin / pharmacology
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology


  • NF-kappa B
  • Nerve Growth Factors
  • Nuclear Proteins
  • Oligodeoxyribonucleotides
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Tretinoin
  • Chloramphenicol O-Acetyltransferase
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate