Induction of apoptosis by p75 neurotrophin receptor in human neuroblastoma cells

Abstract

The low-affinity nerve growth factor receptor p75^NTR belongs to a membrane receptor superfamily whose members, in certain cell types, are able to transduce an apoptotic signal. To investigate the effect of p75^NTR expression in neuroblastoma cells, we transfected the p75^NTR cDNA into SK-N-BE cells, a neuroblastoma cell line that lacks expression of both p75^NTR and TrkA. Cell clones expressing elevated levels of p75^NTR showed a high degree of cell death by apoptosis, even in serum-supplemented medium. Moreover, the level of apoptosis correlated directly with the expression level of the receptor, indicating that p75^NTR could activate the cell death program by itself. Clones expressing p75^NTR showed a dramatic increase of cell death when switched into serum-free medium; these cultures rapidly extinguished. This apoptotic effect was greatly inhibited by NGF treatment. Our results support the hypothesis that p75^NTR, when it is not bound by NGF, may play a role in neuronal selection during embryonic development and suggest that neuroblastomas may arise from immature neuroblasts that escape programmed cell death. Therefore, the loss of p75^NTR expression in developing neural crest cells might be a primary event in the genesis of neuroblastoma.