title: Aberrant expression of the transcription factor Twist in adult T-cell leukemia.
abstract: Adult T-cell leukemia (ATL) is a T-cell malignancy etiologically associated with human T-cell leukemia virus type 1 (HTLV-1). Twist, a highly conserved basic helix-loop-helix transcription factor, is a newly identified oncogene. However, there are no reports on Twist expression in ATL. To define the role of Twist in leukemogenesis of ATL, we examined its expression in T-cell lines and PBMC. HTLV-1-infected T-cell lines and ATL cells expressed high levels of Twist compared with uninfected T-cell lines and normal PBMC. Immunohistochemistry showed immunostaining for Twist in ATL cells in ATL lymph nodes and skin lesions. Infection of normal PBMC with HTLV-1 induced Twist expression. Induction of the viral protein Tax in a human T-cell line led to upregulation of Twist. Tax-induced Twist expression involved the NF-kappaB and CREB signaling pathways. Twist augmented Tax-mediated HTLV-1 LTR and NF-kappaB activation. Short interfering RNA against Twist inhibited cell growth of HTLV-1-infected T-cell lines and downregulation of Twist expression in an HTLV-1-infected T-cell line inhibited the expression of Akt1, interleukin-2 receptor alpha chain, and Tax as well as the known target genes of Twist, YB-1 and Akt2. In conclusion, the results suggest that Tax-induced induction of Twist contributes to leukemogenesis of ATL.
authors.affiliation: Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan.
authors.forename: Hiroe
authors.initials: H
authors.lastname: Tanji
authors.forename: Chie
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authors.lastname: Ishikawa
authors.forename: Shigeki
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authors.lastname: Sawada
authors.forename: Sawako
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authors.lastname: Nakachi
authors.forename: Reika
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authors.forename: Takehiro
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authors.lastname: Matsuda
authors.forename: Taeko
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authors.lastname: Okudaira
authors.forename: Jun-Nosuke
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authors.lastname: Uchihara
authors.forename: Kazuiku
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authors.lastname: Ohshiro
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authors.lastname: Tanaka
authors.forename: Masachika
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authors.lastname: Senba
authors.forename: Hiroshi
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authors.lastname: Uezato
authors.forename: Koichi
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authors.lastname: Ohshima
authors.forename: Madeleine
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authors.lastname: Duc Dodon
authors.forename: Kou-Juey
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authors.lastname: Wu
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authors.lastname: Mori