CILIARY NEUROTROPHIC FACTOR-INDUCED GENE-EXPRESSION IN HUMAN NEUROBLASTOMA CELL-LINES

We have analyzed the response of the human neuroblastoma cell lines SK -N-SH (clone SY5Y) and SK-N-BE to the ciliary neurotrophic factor CNTF . In both cell lines CNTF induced the expression of the mRNA for two t ranscription factors, c-fos and NGF1A. The induction was rapid and tra nsient reaching a maximum between 30 and 60 min after exposure to CNTF ;and subsequently declining. The level of induction of both c-fos and NGF1A mRNAs was much higher in SK-N-BE neuroblastoma cells compared to the SY5Y. Both cells express comparable levels of the transcript for the CNTF receptor-alpha. This mRNA was down regulated after 5 days of CNTF stimulation in both cell lines. CNTF also induced increased level s of the transcript for the growth cone associated protein GAP43 in SK -N-BE, but not in SY5Y cells. Induction followed a slower kinetic comp ared to that observed for c-fos and NGF1A. In fact, the GAP43 mRNA lev els increased during 2 days of exposure to CNTF. Morphological analysi s of CNTF treated cells showed that SK-N-BE undergo significant differ entiation in response to CNTF (increased number of cells with neurites and increased neurite length) while SY5Y did not show appreciable mor phological differentiation. These data shows that CNTF may elicit diff erent response in neuroblastoma cell lines.