Linked Life Data

12970762

Source:http://linkedlifedata.com/resource/pubmed/id/12970762

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2003-10-24
pubmed:abstractText
XIAP is a member of the inhibitors-of-apoptosis family of proteins, which inhibit caspases and block cell death, with prognostic importance in AML. Here we demonstrate that cytokines regulate the expression of XIAP in leukemic cell lines and primary AML blasts. Inhibition of phosphatidylinositol-3 kinase (PI3K) with LY294002 and of the mitogen-activated protein kinase (MAPK) cascade by PD98059 resulted in decreased XIAP levels (34+/-8.7 and 23+/-5.7%, respectively). We then generated OCI-AML3 cells with constitutively phosphorylated Akt (p473-Akt) by retroviral gene transfer. Neither these nor Akt inhibitor-treated OCI-AML3 cells showed changes in XIAP levels, suggesting that XIAP expression is regulated by PI3K downstream effectors other than Akt. The induction of XIAP expression by cytokines through PI3K/MAPK pathways is consistent with its role in cell survival. Exposure of leukemic cells to chemotherapeutic agents decreased XIAP protein levels by caspase-dependent XIAP cleavage. Targeting XIAP by XIAP antisense oligonucleotide resulted in downregulation of XIAP, activation of caspases and cell death, and sensitized HL-60 cells to Ara-C. Our results suggest that XIAP is regulated by cytokines through PI3K, and to a lesser degree through MAPK pathways. Selective downregulation of XIAP expression might be of therapeutic benefit to leukemic patients.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0887-6924
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2081-9
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:12970762-Base Sequence, pubmed-meshheading:12970762-Blast Crisis, pubmed-meshheading:12970762-Cell Survival, pubmed-meshheading:12970762-Cytokines, pubmed-meshheading:12970762-DNA Primers, pubmed-meshheading:12970762-Enzyme Inhibitors, pubmed-meshheading:12970762-Gene Expression Regulation, Neoplastic, pubmed-meshheading:12970762-Humans, pubmed-meshheading:12970762-Leukemia, Myeloid, Acute, pubmed-meshheading:12970762-MAP Kinase Signaling System, pubmed-meshheading:12970762-Oligodeoxyribonucleotides, Antisense, pubmed-meshheading:12970762-Phosphatidylinositol 3-Kinases, pubmed-meshheading:12970762-Proteins, pubmed-meshheading:12970762-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:12970762-Tumor Cells, Cultured, pubmed-meshheading:12970762-X-Linked Inhibitor of Apoptosis Protein, pubmed-meshheading:12970762-Zinc Fingers
pubmed:year
2003
pubmed:articleTitle
Regulation and targeting of antiapoptotic XIAP in acute myeloid leukemia.
pubmed:affiliation
The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.