Source:http://linkedlifedata.com/resource/pubmed/id/18006809
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
22
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pubmed:dateCreated |
2007-11-16
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pubmed:abstractText |
N-MYC encodes a basic helix-loop-helix/leucine zipper (bHLH/LZ) transcription factor that is frequently overexpressed in human neuroblastoma. N-MYC overexpression has also been reported in human acute myeloid leukemias (AML), which we show here is a frequent event. Myeloid cells in N-Myc-overexpressing mouse bone marrow hyperproliferate but those in c-MYC-overexpressing bone marrow do not. The NH(2)-terminal transactivation domain, nuclear localization signal, and bHLH/LZ domain of N-Myc are essential for this effect. Microarray analysis revealed 969 differentially expressed genes between N-Myc- and c-MYC-overexpressing myeloid cells. N-Myc-overexpressing cells showed decreased transforming growth factor beta signaling and increased c-Jun-NH(2)-kinase signaling, both of which are associated with proliferation and leukemic transformation of myeloid cells. Mice transplanted with bone marrow expressing wild-type N-Myc developed clonal and transplantable AML after approximately 1 month; those transplanted with bone marrow expressing mutant N-Myc did not. Twist, a known suppressor of the p19Arf/p53 pathway, was up-regulated in all tumors. These results show that N-Myc overexpression is highly oncogenic in mouse myeloid cells and suggest that N-MYC up-regulation contributes to human myeloid leukemogenesis.
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pubmed:grant | |
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 |
Nov
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pubmed:issn |
1538-7445
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
67
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10677-85
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18006809-Animals,
pubmed-meshheading:18006809-Bone Marrow Cells,
pubmed-meshheading:18006809-Cell Proliferation,
pubmed-meshheading:18006809-Cell Separation,
pubmed-meshheading:18006809-Cell Transformation, Neoplastic,
pubmed-meshheading:18006809-Gene Expression Regulation, Leukemic,
pubmed-meshheading:18006809-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:18006809-Leukemia, Myeloid, Acute,
pubmed-meshheading:18006809-Mice,
pubmed-meshheading:18006809-Myeloid Cells,
pubmed-meshheading:18006809-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:18006809-Protein Structure, Tertiary,
pubmed-meshheading:18006809-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:18006809-Signal Transduction,
pubmed-meshheading:18006809-Transforming Growth Factor beta
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pubmed:year |
2007
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pubmed:articleTitle |
Overexpression of N-Myc rapidly causes acute myeloid leukemia in mice.
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pubmed:affiliation |
Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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