Over-expression of Flt3 induces NF-kappaB pathway and increases the expression of IL-6.
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-kappaB), which is a target molecule of these kinase pathways. In BaF3 cells stably expressing Flt3, a NF-kappaB-responsive reporter was upregulated and its target gene, IL-6, was increased by the involvement of Flt3-ERK/MAPK-NF-kappaB 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-kappaB pathway.
Department of Clinical Laboratory Medicine, Tohoku University School of Medicine, 1-1 Seiryou-machi, Aobaku, Sendai 980-8574, Japan. shintak@mail.tains.tohoku.ac.jp
Shinichiro
S
Takahashi
Hideo
H
Harigae
Keiko Kumura
KK
Ishii
Mitsue
M
Inomata
Tohru
T
Fujiwara
Hisayuki
H
Yokoyama
Kenichi
K
Ishizawa
Junichi
J
Kameoka
Jonathan D
JD
Licht
Takeshi
T
Sasaki
Mitsuo
M
Kaku
D000818:Animals; D002460:Cell Line; D015973:Gene Expression Regulation, Leukemic; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D015854:Up-Regulation; D051941:fms-Like Tyrosine Kinase 3
D015850:Interleukin-6; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3