Topic
Differentiating Neuroblastoma
About: Differentiating Neuroblastoma is a research topic. Over the lifetime, 66 publications have been published within this topic receiving 1558 citations.
Papers published on a yearly basis
Papers
TL;DR: The data indicate that p21WAF1 expression is required for survival of these differentiating neuroblastoma cells, and the problem of neuronal differentiation can now be understood in the context of negative regulators of the cell cycle.
Abstract: We are employing recent advances in the understanding of the cell cycle to study the inverse relationship between proliferation and neuronal differentiation. Nerve growth factor and aphidicolin, an inhibitor of DNA polymerases, synergistically induce neuronal differentiation of SH-SY5Y neuroblastoma cells and the expression of p21WAF1, an inhibitor of cyclin-dependent kinases. The differentiated cells continue to express p21WAF1, even after removal of aphidicolin from the culture medium. The p21WAF1 protein coimmunoprecipitates with cyclin E and inhibits cyclin E-associated protein kinase activity. Each of three antisense oligonucleotides complementary to p21WAF1 mRNA partially blocks expression of p21WAF1 and promotes programmed cell death. These data indicate that p21WAF1 expression is required for survival of these differentiating neuroblastoma cells. Thus, the problem of neuronal differentiation can now be understood in the context of negative regulators of the cell cycle.
238 citations
TL;DR: Data show that functional sympathetic neuronal differentiation of neuroblastoma cells is associated with transient activation of HES‐1 and down‐regulation of HASH‐1 expression.
Abstract: Neuroblastoma is a childhood tumor that originates from the sympathetic nervous system. The tumor cells have embryonic features, presumably as a consequence of an impaired capacity to respond to signals and transcriptional control mechanisms operating during normal differentiation. Two basic helix-loop-helix transcription factors, human achaete-scute homologue-1 (HASH-1) and hairy/enhancer of split homologue-1 (HES-1), are crucial for proper development of some neuronal cells. Here, their potential roles during sympathetic differentiation of human neuroblastoma cells have been investigated. In all tested protocols for induction of differentiation of SH-SY5Y and SK-N-BE(2) neuroblastoma cells, HASH-1 expression was rapidly decreased with a concomitant, often transient, increase in HES-1 expression. In gel mobility shift assays, using extracts from neuroblastoma cells, HES-1 bound to an oligonucleotide corresponding to a sequence in the HASH-1 promoter including the so-called N-box, suggesting that the transiently increased HES-1 activity in differentiating neuroblastoma cells is involved in down-regulation of HASH-1. Constitutive expression of the intracellular domain of Notch1, which activates the HES-1 promoter in SH-SY5Y cells, inhibited spontaneous and induced morphological differentiation of these neuroblastoma cells. Our data show that functional sympathetic neuronal differentiation of neuroblastoma cells is associated with transient activation of HES-1 and down-regulation of HASH-1 expression.
61 citations
TL;DR: The results suggest that the inhibition of axon production and maintenance by CPF in differentiating N2a cells may involve multiple targets, which are different under co- and post-differentiation conditions.
59 citations
TL;DR: Thirty-nine teratogenic and 18 nonteratogenic compounds were tested using an assay based on the ability of agents to interfere with normal growth and differentiation of murine neuroblastoma cells (clone N1E-115) in culture, with the lowest effective dose not being highly toxic.
Abstract: Thirty-nine teratogenic and 18 nonteratogenic compounds were tested using an assay based on the ability of agents to interfere with normal growth and differentiation of murine neuroblastoma cells (clone N1E-115) in culture. Induction of differentiation in cells under growth-promoting conditions and inhibition of differentiating cells over a period of 7 days was dose-dependent, with the lowest effective dose not being highly toxic. Eighty-six percent of the compounds were correctly identified by the assay. The proportions of both false negatives (10%) and false positives (22%) were of the same order or better than in current, comparable tests. The possibilities offered by the system in rapid screening for teratogenic potential of environmental agents are discussed.
58 citations
TL;DR: It is concluded that moderate HASH-1 expression does not compromise the capacity of the neuroblastoma cells to differentiate in response to differentiation-inducing agents.
52 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 3 |
| 2020 | 1 |
| 2018 | 2 |
| 2017 | 2 |
| 2015 | 1 |
| 2014 | 1 |