Overexpression of BETA2/NeuroD induces neurite outgrowth in F11 neuroblastoma cells.
BETA2/NeuroD, a basic helix-loop-helix (bHLH) transcription factor, has been shown to play important roles in the development of the nervous system and the maintenance and formation of pancreatic and enteroendocrine cells. The gain of function of BETA2/NeuroD in neurogenesis has been shown in Xenopus embryos. In this study, we investigated the neurogenic potential of BETA2/NeuroD using neuroblastoma cell line, F11, which could be induced to differentiate into neurons in the presence of cAMP. To induce or block the expression of BETA2/NeuroD, expression vectors for the full-length and a C-terminal deletion mutant of BETA2 were constructed and their transactivation potential was verified using reporter genes containing the insulin promoter sequences. Overexpression of BETA2 with full-length construct induced neurite outgrowth in F11 cells in the absence of cAMP. In contrast, the C-terminal deletion mutant, BETA2(1--233), which has dominant negative activity, inhibited neurite outgrowth induced by cAMP in F11 cells. These results indicate that BETA2/NeuroD plays an important role in terminal differentiation of neuroblastoma cells. They also imply that BETA2/NeuroD or related bHLH factors plays an essential role for differentiation of F11 neuroblastoma cells.
Cho
J H
JH
Department of Anatomy, Brain Disease Research Center, School of Medicine, Ajou University, Suwon, South Korea.
Kwon
I S
IS
Kim
S
S
Ghil
S H
SH
Tsai
M J
MJ
Kim
Y S
YS
Lee
Y D
YD
Suh-Kim
H
H
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D000242:Cyclic AMP / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D005799:Genes, Dominant; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D018257:Helix-Loop-Helix Motifs; D007328:Insulin / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D051381:Rats; D017384:Sequence Deletion; D014162:Transfection; D014407:Tumor Cells, Cultured
D051792:Basic Helix-Loop-Helix Proteins; D000242:Cyclic AMP; D007328:Insulin; D009419:Nerve Tissue Proteins; C093564:Neurogenic differentiation factor 1