FLT3 regulates beta-catenin tyrosine phosphorylation, nuclear localization, and transcriptional activity in acute myeloid leukemia cells.

FLT3 regulates beta-catenin tyrosine phosphorylation, nuclear localization, and transcriptional activity in acute myeloid leukemia cells. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

FLT3 regulates beta-catenin tyrosine phosphorylation, nuclear localization, and transcriptional activity in acute myeloid leukemia cells. Abstract Text:

T Kajiguchi,E J Chung,S Lee,A Stine,H Kiyoi,T Naoe,M J Levis,L Neckers,J B Trepel,T Kajiguchi,E J Chung,S Lee,A Stine,H Kiyoi,T Naoe,M J Levis,L Neckers,J B Trepel,

Deregulated accumulation of nuclear beta-catenin enhances transcription of beta-catenin target genes and promotes malignant transformation. Recently, acute myeloid leukemia (AML) cells with activating mutations of FMS-like tyrosine kinase-3 (FLT3) were reported to display elevated beta-catenin-dependent nuclear signaling. Tyrosine phosphorylation of beta-catenin has been shown to promote its nuclear localization. Here, we examined the causal relationship between FLT3 activity and beta-catenin nuclear localization. Compared to cells with wild-type FLT3 (FLT3-WT), cells with the FLT3 internal tandem duplication (FLT3-ITD) and tyrosine kinase domain mutation (FLT3-TKD) had elevated levels of tyrosine-phosphorylated beta-catenin. Although beta-catenin was localized mainly in the cytoplasm in FLT3-WT cells, it was primarily nuclear in FLT3-ITD cells. Treatment with FLT3 kinase inhibitors or FLT3 silencing with RNAi decreased beta-catenin tyrosine phosphorylation and nuclear localization. Conversely, treatment of FLT3-WT cells with FLT3 ligand increased tyrosine phosphorylation and nuclear accumulation of beta-catenin. Endogenous beta-catenin co-immunoprecipitated with endogenous activated FLT3, and recombinant activated FLT3 directly phosphorylated recombinant beta-catenin. Finally, FLT3 inhibitor decreased tyrosine phosphorylation of beta-catenin in leukemia cells obtained from FLT3-ITD-positive AML patients. These data demonstrate that FLT3 activation induces beta-catenin tyrosine phosphorylation and nuclear localization, and thus suggest a mechanism for the association of FLT3 activation and beta-catenin oncogeneic signaling in AML.

FLT3 regulates beta-catenin tyrosine phosphorylation, nuclear localization, and transcriptional activity in acute myeloid leukemia cells. Publishing Authors By Initials

T Kajiguchi,EJ Chung,S Lee,A Stine,H Kiyoi,T Naoe,MJ Levis,L Neckers,JB Trepel,T Kajiguchi,EJ Chung,S Lee,A Stine,H Kiyoi,T Naoe,MJ Levis,L Neckers,JB Trepel,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

FLT3 regulates beta-catenin tyrosine phosphorylation, nuclear localization, and transcriptional activity in acute myeloid leukemia cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Leukemia : official journal of the Leukemia Societ

VOLUME: 21

Page Numbers: 2476-84

Journal Abbreviation: Leukemia

ISSN: 1476-5551

DAY: 13

MONTH: 09

YEAR: 2007

FLT3 regulates beta-catenin tyrosine phosphorylation, nuclear localization, and transcriptional activity in acute myeloid leukemia cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8704895

FLT3 regulates beta-catenin tyrosine phosphorylation, nuclear localization, and transcriptional activity in acute myeloid leukemia cells. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: FLT3 regulates beta-catenin tyrosine phosphorylation, nuclear localization, and transcriptional activity in acute myeloid leukemia cells. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for FLT3 regulates beta-catenin tyrosine phosphorylation, nuclear localization, and transcriptional activity in acute myeloid leukemia cells.

AFFILIATION: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. tomokaji@med.nagoya-u.ac.jp

Country: England

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Leukemia

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

FLT3 regulates beta-catenin tyrosine phosphorylation, nuclear localization, and transcriptional activity in acute myeloid leukemia cells Related Publications

• FLT3 regulates beta-catenin tyrosine phosphorylation, nuclear localization, and transcriptional activity in acute myeloid leukemia cells.
• Histone deacetylase inhibitors in cancer therapy.
• Rosette formation of pig peripheral blood lymphocytes with sheep red blood cells.
• Vectors selected from adeno-associated viral display peptide libraries for leukemia cell-targeted cytotoxic gene therapy.