Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-2-4
pubmed:abstractText
In most postmitotic neurons, expression or activation of proteins that stimulate cell cycle progression or DNA replication results in apoptosis. One potential exception to this generalization is neuroblastoma (NB), a tumor derived from the sympathoadrenal lineage. NBs often express high levels of N-myc, a proto-oncogene that can potently activate key components of the cell cycle machinery. Here, we show that in postmitotic sympathetic neurons, N-myc can induce S-phase entry while protecting neurons from death caused by aberrant cell cycle reentry. Specifically, these experiments demonstrate that expression of N-myc at levels similar to those in NBs caused sympathetic neurons to reenter S-phase, as monitored by 5-bromo-2-deoxyuridine incorporation and expression of cell cycle regulatory proteins, and rescued them from apoptosis induced by withdrawal of their obligate survival factor, nerve growth factor. The N-myc-induced cell cycle entry, but not enhanced survival, was inhibited by coexpression of a constitutively hypophosphorylated form of the retinoblastoma tumor suppressor protein, suggesting that these two effects of N-myc are mediated by separate pathways. In contrast, N-myc did not cause S-phase entry in postmitotic cortical neurons. Thus, N-myc both selectively causes sympathetic neurons to reenter the cell cycle and protects them from apoptosis, potentially contributing to their transformation to NBs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
815-24
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11826111-Adenoviridae, pubmed-meshheading:11826111-Animals, pubmed-meshheading:11826111-Apoptosis, pubmed-meshheading:11826111-Bromodeoxyuridine, pubmed-meshheading:11826111-Cell Survival, pubmed-meshheading:11826111-Cells, Cultured, pubmed-meshheading:11826111-Cerebral Cortex, pubmed-meshheading:11826111-Gene Expression, pubmed-meshheading:11826111-Genetic Vectors, pubmed-meshheading:11826111-Humans, pubmed-meshheading:11826111-Mice, pubmed-meshheading:11826111-Mitosis, pubmed-meshheading:11826111-Nerve Growth Factor, pubmed-meshheading:11826111-Neuroblastoma, pubmed-meshheading:11826111-Neurons, pubmed-meshheading:11826111-Phosphorylation, pubmed-meshheading:11826111-Proto-Oncogene Proteins c-myc, pubmed-meshheading:11826111-Rats, pubmed-meshheading:11826111-Rats, Sprague-Dawley, pubmed-meshheading:11826111-Retinoblastoma Protein, pubmed-meshheading:11826111-S Phase, pubmed-meshheading:11826111-Sympathetic Nervous System, pubmed-meshheading:11826111-Transfection
pubmed:year
2002
pubmed:articleTitle
N-myc promotes survival and induces S-phase entry of postmitotic sympathetic neurons.
pubmed:affiliation
Brain Tumor Research Center and Center for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't