Neurite outgrowth plays a key role in neuronal development and regeneration, and is the hallmark assay for the effects of
neurotrophic factors such as
nerve growth factor (
NGF). However, measuring neurite outgrowth is a slow and resource-intensive process. We therefore wanted to identify surrogate
biomarkers for neurite outgrowth activity by gene expression analysis in SH-O10 cells, a subclone of the human SH-SY5Y
neuroblastoma cell line but with much higher
NGF-induced neurite outgrowth activity. Microarray analysis identified seven genes where
mRNA levels were changed.
NGF-induced decreases in levels of two genes, CyclinB2 and BIRC5, were confirmed by quantitative real-time RT-PCR. Levels of
NGF-induced decreases in CyclinB2 and BIRC5
mRNA in several SH-SY5Y subclones with different neurite outgrowth responses correlated with their neurite outgrowth activities. Decreases in CyclinB2 and BIRC5
mRNA induced by
FK506 or
retinoic acid, both of which exert potentiation of
NGF-induced neurite outgrowth effects but with different mechanisms, also correlated with their neurite outgrowth activities. In conclusion, decreasing levels of CyclinB2 and BIRC5
mRNA strongly correlate with neurite outgrowth activities in terms of
NGF-related effect in SH-SY5Y subclonal cells, and have potential to become quantitative surrogate
biomarkers for measuring
NGF-related neurite outgrowth.