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Transcriptional activation of survivin through the NF‐κB pathway by human T‐cell leukemia virus type I tax
Author(s) -
Kawakami Hirochika,
Tomita Mariko,
Matsuda Takehiro,
Ohta Takao,
Tanaka Yuetsu,
Fujii Masahiro,
Hatano Masahiko,
Tokuhisa Takeshi,
Mori Naoki
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20954
Subject(s) - survivin , apoptosis , inhibitor of apoptosis , cancer research , carcinogenesis , transfection , biology , downregulation and upregulation , cell culture , nf κb , cancer , programmed cell death , gene , genetics
Survivin, a unique member of the inhibitor of apoptosis protein family, is overexpressed in many cancers and considered to play an important role in oncogenesis. We previously reported the survivin expression profile in ATL, a CD4‐positive T‐cell malignancy caused by HTLV‐I. HTLV‐I Tax is thought to play an important role in immortalization of T cells. We have shown also that the expression of Tax protected the mouse T‐cell line CTLL‐2 against apoptosis induced by deprivation of IL‐2 and converted its growth from being IL‐2 dependent to being IL‐2 independent through the NF‐κB pathway. In our study, we demonstrate that constitutive expression of survivin was associated with resistance to apoptosis after IL‐2 deprivation in Tax‐expressing CTLL‐2 cells. Transient transfection assays showed that survivin promoter was transactivated by Tax, via the activation of NF‐κB. Pharmacological NF‐κB inhibition resulted in suppression of survivin expression and caused apoptosis of Tax‐expressing CTLL‐2 cells. Our findings suggest that activated NF‐κB signaling contributes directly to malignant progression of ATL by preventing apoptosis, acting through the prosurvival protein survivin. © 2005 Wiley‐Liss, Inc.