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 transcription factors, c-fos and NGF1A. The induction was rapid and transient 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 levels of the transcript for the growth cone associated protein GAP43 in SK-N-BE, but not in SY5Y cells. Induction followed a slower kinetic compared to that observed for c-fos and NGF1A. In fact, the GAP43 mRNA levels increased during 2 days of exposure to CNTF. Morphological analysis of CNTF treated cells showed that SK-N-BE undergo significant differentiation in response to CNTF (increased number of cells with neurites and increased neurite length) while SY5Y did not show appreciable morphological differentiation. These data shows that CNTF may elicit different response in neuroblastoma cell lines.
Rossino
P
P
Department of Genetics, Biology and Medical Chemistry, University of Torino, Italy.
Volpe
G
G
Negro
A
A
Callegaro
L
L
Altruda
F
F
Tarone
G
G
Silengo
L
L
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D020934:Ciliary Neurotrophic Factor; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D051766:Early Growth Response Protein 1; D019922:GAP-43 Protein; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009447:Neuroblastoma; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
D020934:Ciliary Neurotrophic Factor; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D019922:GAP-43 Protein; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D014157:Transcription Factors