Aberrant expression of the transcription factor Twist in adult T-cell leukemia.
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.
Tanji
Hiroe
H
Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan.
Ishikawa
Chie
C
Sawada
Shigeki
S
Nakachi
Sawako
S
Takamatsu
Reika
R
Matsuda
Takehiro
T
Okudaira
Taeko
T
Uchihara
Jun-Nosuke
JN
Ohshiro
Kazuiku
K
Tanaka
Yuetsu
Y
Senba
Masachika
M
Uezato
Hiroshi
H
Ohshima
Koichi
K
Duc Dodon
Madeleine
M
Wu
Kou-Juey
KJ
Mori
Naoki
N