Source:http://linkedlifedata.com/resource/pubmed/id/11826111
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2002-2-4
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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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1529-2401
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
22
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
815-24
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pubmed:dateRevised |
2006-11-15
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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
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pubmed:year |
2002
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pubmed:articleTitle |
N-myc promotes survival and induces S-phase entry of postmitotic sympathetic neurons.
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pubmed:affiliation |
Brain Tumor Research Center and Center for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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