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.
Pharmacology, Pharmakinetics Research Laboratories, Astellas Pharma Inc., Ibaraki, Japan. tomoya.ooe@jp.astellas.com
Tomoya
T
Oe
Takeshi
T
Sasayama
Takeyuki
T
Nagashima
Masakazu
M
Muramoto
Takao
T
Yamazaki
Noriyuki
N
Morikawa
Osamau
O
Okitsu
Shintaro
S
Nishimura
Toshiaki
T
Aoki
Yoshiki
Y
Katayama
Yasuhiro
Y
Kita
D045744:Cell Line, Tumor; D002999:Clone Cells / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D017781:Genes, Immediate-Early; D006801:Humans; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects*; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D020411:Oligonucleotide Array Sequence Analysis; D020917:Receptor, trkA / Q000378:metabolism
D020932:Nerve Growth Factor; D020917:Receptor, trkA