Differences in gene expression profile among SH‐SY5Y neuroblastoma subclones with different neurite outgrowth responses to nerve growth factor

Nerve growth factor (NGF) plays a key role in the differentiation of neurons. In this study, we established three NGF‐induced neurite‐positive (NIN+) subclones that showed high responsiveness to NGF‐induced neurite outgrowth and three NGF‐induced neurite‐negative (NIN–) subclones that abolished NGF‐induced neurite outgrowth from parental SH‐SY5Y cells, and analyzed differences in the NGF signaling cascade. The NIN+ subclones showed enhanced responsiveness to FK506‐mediated neurite outgrowth as well. To clarify the mechanism behind the high frequency of NGF‐induced neurite outgrowth, we investigated differences in NGF signaling cascade among subclones. Expression levels of the NGF receptor TrkA, and NGF‐induced increases in mRNAs for the immediate‐early genes (IEGs) c‐fos and NGF inducible (NGFI) genes NGFI‐A, NGFI‐B and NGFI‐C, were identical among subclones. Microarray analysis revealed that the NIN+ cell line showed a very different gene expression profile to the NIN– cell line, particularly in terms of axonal vesicle‐related genes and growth cone guidance‐related genes. Thus, the difference in NGF signaling cascade between the NIN+ and NIN– cell lines was demonstrated by the difference in gene expression profile. These differentially expressed genes might play a key role in neurite outgrowth of SH‐SY5Y cells in a region downstream from the site of induction of IEGs, or in a novel NGF signaling cascade.

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