Over-expression of Flt3 induces NF-κB pathway and increases the expression of IL-6

Shinichiro Takahashi; Hideo Harigae; Keiko Kumura Ishii; Mitsue Inomata; Tohru Fujiwara; Hisayuki Yokoyama; Kenichi Ishizawa; Junichi Kameoka; Jonathan D. Licht; Takeshi Sasaki; Mitsuo Kaku

doi:10.1016/j.leukres.2005.01.008

Over-expression of Flt3 induces NF-κB pathway and increases the expression of IL-6

Shinichiro Takahashi
, Hideo Harigae
, Keiko Kumura Ishii
, Mitsue Inomata
, Tohru Fujiwara
, Hisayuki Yokoyama
, Kenichi Ishizawa
, Junichi Kameoka
, Jonathan D. Licht
, Takeshi Sasaki
, Mitsuo Kaku

Research output: Contribution to journal › Article › peer-review

46 Scopus citations

Abstract

Activating mutations or over-expression of the Flt3 is prevalent in acute myeloblastic leukemia (AML), associated with activation of Ras/MAP kinase and other signaling pathways. In this study, we addressed the role of Flt3 in the activation of nuclear factor-kappa B (NF-κB), which is a target molecule of these kinase pathways. In BaF3 cells stably expressing Flt3, a NF-κB-responsive reporter was upregulated and its target gene, IL-6, was increased by the involvement of Flt3-ERK/MAPK-NF-κB pathway. Furthermore, we found a modest positive correlation (r = 0.35, p = 0.096) between Flt3 and IL-6 mRNA expression in 24 AML specimens. These results suggest a role of Flt3 over-expression in NF-κB pathway.

Original language	English
Pages (from-to)	893-899
Number of pages	7
Journal	Leukemia Research
Volume	29
Issue number	8
DOIs	https://doi.org/10.1016/j.leukres.2005.01.008
State	Published - Aug 2005

Keywords

AML
Flt3
IL-6
NF-κB

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10.1016/j.leukres.2005.01.008

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@article{3109b0d7fcdf4d8ab270eda8bcf07735,

title = "Over-expression of Flt3 induces NF-κB pathway and increases the expression of IL-6",

abstract = "Activating mutations or over-expression of the Flt3 is prevalent in acute myeloblastic leukemia (AML), associated with activation of Ras/MAP kinase and other signaling pathways. In this study, we addressed the role of Flt3 in the activation of nuclear factor-kappa B (NF-κB), which is a target molecule of these kinase pathways. In BaF3 cells stably expressing Flt3, a NF-κB-responsive reporter was upregulated and its target gene, IL-6, was increased by the involvement of Flt3-ERK/MAPK-NF-κB pathway. Furthermore, we found a modest positive correlation (r = 0.35, p = 0.096) between Flt3 and IL-6 mRNA expression in 24 AML specimens. These results suggest a role of Flt3 over-expression in NF-κB pathway.",

keywords = "AML, Flt3, IL-6, NF-κB",

author = "Shinichiro Takahashi and Hideo Harigae and Ishii, \{Keiko Kumura\} and Mitsue Inomata and Tohru Fujiwara and Hisayuki Yokoyama and Kenichi Ishizawa and Junichi Kameoka and Licht, \{Jonathan D.\} and Takeshi Sasaki and Mitsuo Kaku",

note = "Funding Information: Authors thank for Dr. G. Gilliland for providing MSCV-Flt3-GFP plasmid and Dr. H. Schepers for helpful suggestions. We also thank for Drs. M. Yamada, Y. Tohmiya, M. Seki and Y. Okitsu for stimulating discussions. This work is supported in part by Japan Society of Promotion of Science (to S.T.), Kurozumi Medical Foundation (to S.T.), Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (to H.H., T.S.). ",

year = "2005",

month = aug,

doi = "10.1016/j.leukres.2005.01.008",

language = "English",

volume = "29",

pages = "893--899",

journal = "Leukemia Research",

issn = "0145-2126",

publisher = "Elsevier Ltd.",

number = "8",

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T1 - Over-expression of Flt3 induces NF-κB pathway and increases the expression of IL-6

AU - Takahashi, Shinichiro

AU - Harigae, Hideo

AU - Ishii, Keiko Kumura

AU - Inomata, Mitsue

AU - Fujiwara, Tohru

AU - Yokoyama, Hisayuki

AU - Ishizawa, Kenichi

AU - Kameoka, Junichi

AU - Licht, Jonathan D.

AU - Sasaki, Takeshi

AU - Kaku, Mitsuo

N1 - Funding Information: Authors thank for Dr. G. Gilliland for providing MSCV-Flt3-GFP plasmid and Dr. H. Schepers for helpful suggestions. We also thank for Drs. M. Yamada, Y. Tohmiya, M. Seki and Y. Okitsu for stimulating discussions. This work is supported in part by Japan Society of Promotion of Science (to S.T.), Kurozumi Medical Foundation (to S.T.), Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (to H.H., T.S.).

PY - 2005/8

Y1 - 2005/8

N2 - Activating mutations or over-expression of the Flt3 is prevalent in acute myeloblastic leukemia (AML), associated with activation of Ras/MAP kinase and other signaling pathways. In this study, we addressed the role of Flt3 in the activation of nuclear factor-kappa B (NF-κB), which is a target molecule of these kinase pathways. In BaF3 cells stably expressing Flt3, a NF-κB-responsive reporter was upregulated and its target gene, IL-6, was increased by the involvement of Flt3-ERK/MAPK-NF-κB pathway. Furthermore, we found a modest positive correlation (r = 0.35, p = 0.096) between Flt3 and IL-6 mRNA expression in 24 AML specimens. These results suggest a role of Flt3 over-expression in NF-κB pathway.

AB - Activating mutations or over-expression of the Flt3 is prevalent in acute myeloblastic leukemia (AML), associated with activation of Ras/MAP kinase and other signaling pathways. In this study, we addressed the role of Flt3 in the activation of nuclear factor-kappa B (NF-κB), which is a target molecule of these kinase pathways. In BaF3 cells stably expressing Flt3, a NF-κB-responsive reporter was upregulated and its target gene, IL-6, was increased by the involvement of Flt3-ERK/MAPK-NF-κB pathway. Furthermore, we found a modest positive correlation (r = 0.35, p = 0.096) between Flt3 and IL-6 mRNA expression in 24 AML specimens. These results suggest a role of Flt3 over-expression in NF-κB pathway.

KW - AML

KW - Flt3

KW - IL-6

KW - NF-κB

UR - https://www.scopus.com/pages/publications/20544467182

U2 - 10.1016/j.leukres.2005.01.008

DO - 10.1016/j.leukres.2005.01.008

M3 - Article

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AN - SCOPUS:20544467182

SN - 0145-2126

VL - 29

SP - 893

EP - 899

JO - Leukemia Research

JF - Leukemia Research

IS - 8

ER -

Over-expression of Flt3 induces NF-κB pathway and increases the expression of IL-6

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Keywords

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