Here we demonstrate that NGF-but not neurotrophin-3 (NT-3) or brain-derived neurotrophic factor (BDNF)-induced apoptosis in p75NTR-expressing human neuroblastoma SK-N-MC cells.BDNF prevented NGF-induced apoptosis.
The recent advances in neuroblastoma research have revealed that the neurotrophin signals, especially those through nerve growth factor and its receptor, TrkA, play an important role in regulating the regression of neuroblastoma.
In a series of studies using, in turn, neuroblastoma cell lines that express only p75, mutant NGF species that bind selectively to either p75 or trkA, and a polyclonal antibody that binds to the NGF-binding domain of p75, we demonstrate that NGF binding to p75 is both necessary and sufficient for the abrogation of apoptosis in neuroblastoma cells treated with antimitotic agents.
Human neuroblastoma SH-SY5Y and IMR32 cells and rat phaeochromocytoma PC12 cells were used as an in vitro system for neuronal differentiation and were induced to differentiate in the presence of retinoic acid, a combination of dibutyryl cAMP and 5-bromodeoxyuridine, and nerve growth factor respectively.
Thus, the restoration of the NGF-induced differentiation pathway by exogenous TRK-A presents a system of NGF-responsive human cultured cells and focuses attention on the trk-A protein and its function or malfunction in neuroblastoma.
The expression of gp140TRK-A mRNA correlates with distinct biologic and clinical subsets of neuroblastoma, which suggests a role for the high-affinity nerve growth factor receptors in determining the phenotype of neuroblastoma.
We have used the human neuroblastoma cell line SH-SY5Y as a model system to investigate the expression and regulation of the receptors for brain-derived neurotrophic factor (BDNF), a member of the nerve growth factor (NGF) family of neurotrophins.
A tumor with a functional nerve growth factor receptor may be dependent on the neurotrophin nerve growth factor for survival and may regress in its absence, allowing a new approach to the treatment of certain patients with neuroblastoma.
Nerve growth factor (NGF), essential for differentiation and survival of sympathetic neurons is suggested to play a role in differentiation or regression of neuroblastoma.
The simultaneous presence of mRNA related to both forms of the NGF receptor, while not proving the presence of a functional receptor, indicates the existence of a sub-set of neuroblastoma cells potentially responsive to NGF.
Human SH-SY5Y neuroblastoma cells treated with retinoic acid, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or nerve growth factor differentiated morphologically to neuronlike cells with increased amounts of neurofilament protein and mRNA.