Linked Life Data

12944913

Source:http://linkedlifedata.com/resource/pubmed/id/12944913

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
36
pubmed:dateCreated
2003-8-28
pubmed:abstractText
Overexpression of proto-oncogene c-jun and constitutive activation of the Jun N-terminal kinase (JNK) signaling pathway have been implicated in the leukemic transformation process. However, c-jun expression and the role of the JNK signaling pathway have not been investigated in primary acute myeloid leukemia (AML) cells with frequently observed balanced rearrangements such as t(8;21). In the present study, we report elevated c-jun mRNA expression in AML patient bone marrow cells with t(8;21), t(15;17) or inv(16), and a high correlation in mRNA expression levels of AML1-ETO and c-jun within t(8;21)-positive AML patient cells. In myeloid U937 cells, c-jun mRNA and protein expression increase upon inducible expression of AML1-ETO. AML1-ETO transactivates the human c-jun promoter through the proximal activator protein (AP-1) site by activating the JNK pathway. Overexpression of JNK-inhibitor JIP-1 and chemical JNK inhibitors reduce the transactivation capacity of AML1-ETO on the c-jun promoter and the proapoptotic function of AML1-ETO in U937 cells. An autocrine mechanism involving granulocyte-colony stimulating factor (G-CSF) and G-CSF receptor (G-CSF-R) might participate in AML1-ETO mediated JNK-signaling, because AML1-ETO induces G-CSF and G-CSF-R expression, and G-CSF-R-neutralizing antibodies reduce AML1-ETO-induced JNK phosphorylation. These data suggest a model in which AML1-ETO induces proto-oncogene c-jun expression via the proximal AP-1 site of the c-jun promoter in a JNK-dependent manner.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5646-57
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12944913-Chromosomes, Human, Pair 21, pubmed-meshheading:12944913-Chromosomes, Human, Pair 8, pubmed-meshheading:12944913-Core Binding Factor Alpha 2 Subunit, pubmed-meshheading:12944913-Genes, jun, pubmed-meshheading:12944913-Granulocyte Colony-Stimulating Factor, pubmed-meshheading:12944913-Humans, pubmed-meshheading:12944913-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:12944913-Leukemia, Myeloid, Acute, pubmed-meshheading:12944913-Mitogen-Activated Protein Kinases, pubmed-meshheading:12944913-Oncogene Proteins, Fusion, pubmed-meshheading:12944913-Phosphorylation, pubmed-meshheading:12944913-Promoter Regions, Genetic, pubmed-meshheading:12944913-Proto-Oncogene Proteins c-jun, pubmed-meshheading:12944913-Signal Transduction, pubmed-meshheading:12944913-Transcription Factor AP-1, pubmed-meshheading:12944913-Transcription Factors, pubmed-meshheading:12944913-Transcriptional Activation, pubmed-meshheading:12944913-Translocation, Genetic, pubmed-meshheading:12944913-U937 Cells
pubmed:year
2003
pubmed:articleTitle
The fusion protein AML1-ETO in acute myeloid leukemia with translocation t(8;21) induces c-jun protein expression via the proximal AP-1 site of the c-jun promoter in an indirect, JNK-dependent manner.
pubmed:affiliation
Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University Munich, Germany.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't