Activation of Nuclear Factor KB in Human Neuroblastoma Cell Lines

: The nuclear factor KB (NF-kB) is a eukaryotic transcription factor. In B cells and macrophages it is constitutively present in cell nuclei, whereas in many other cell types, NF-KB translocates from cytosol to nucleus as a result of transduction by tumor necrosis factor α (TNFα), phorbol ester, and other polyclonal signals. Using neuro-blastoma cell lines as models, we have shown that in neural cells NF-KB was present in the cytosol and translocated into nuclei as a result of TNFa treatment. The TNFα-activated NF-KB was transcriptionally functional. NF-KB activation by TNFα 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-KB, but only in that particular cell line. In a NGF-responsive rat pheochromocytoma cell line, PC12, PMA activated NF-KB, 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-kB 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-KB was not activated by retinoic acid, which induced morphological differentiation of all the neuroblastoma cell lines used in the present study. Thus, NF-KB activation was not required for neuroblastoma cell differentiation. Furthermore, the results obtained with TNFα proved that NF-KB activation was not sufficient for induction of neuroblastoma differentiation.