Identification of annexin 1 as a PU.1 target gene in leukemia cells

Iseki, Yuko; Imoto, Akemi; Okazaki, Toshio; Harigae, Hideo; Takahashi, Shinichiro

doi:10.1016/j.leukres.2009.04.010

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Volume 33, Issue 12 , Pages 1658-1663, December 2009

Identification of annexin 1 as a PU.1 target gene in leukemia cells

Yuko Iseki
- Division of Molecular Hematology, Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Sagamihara City, Kanagawa 228-8555, Japan
- These authors contributed equally to this work.
Akemi Imoto
- Division of Molecular Hematology, Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Sagamihara City, Kanagawa 228-8555, Japan
- These authors contributed equally to this work.
Toshio Okazaki
- Division of Molecular Hematology, Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Sagamihara City, Kanagawa 228-8555, Japan
- Division of Hematology, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Sagamihara city, Kanagawa 228-8555, Japan
Hideo Harigae
- Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Japan
Shinichiro Takahashi
- Division of Molecular Hematology, Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Sagamihara City, Kanagawa 228-8555, Japan
- Division of Hematology, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Sagamihara city, Kanagawa 228-8555, Japan
- Corresponding author at: Division of Molecular Hematology, Kitasato University Graduate School of Medical Sciences, Division of Hematology, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Sagamihara City, Kanagawa 228-8555, Japan. Tel.: +81 42 778 8216; fax: +81 42 778 8216.

Received 19 January 2009; received in revised form 12 March 2009; accepted 7 April 2009. published online 07 March 2011.

Abstract

To identify PU.1 downstream target genes, we first established PU.1-knockdown K562 (K562PU.1KD) cells expressing reduced levels of PU.1 by stably transfected PU.1 siRNAs. From microarray analysis, we found that several genes including annexin 1 were markedly induced in K562PU.1KD cells. Annexin 1 is a calcium- and phospholipid-binding protein and increased expression leads to the constitutive activation of extracellular signal-regulated kinase (ERK). Consistent with this, we observed constitutive activation of ERK in K562PU.1KD cells. Furthermore, we revealed the mRNA expression of annexin 1 was negatively correlated with PU.1 mRNA expression in 43 primary AML specimens (R=−0.31, p<0.042).