title: Transcriptional activation of survivin through the NF-kappaB pathway by human T-cell leukemia virus type I tax.
abstract: 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-kappaB 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-kappaB. Pharmacological NF-kappaB inhibition resulted in suppression of survivin expression and caused apoptosis of Tax-expressing CTLL-2 cells. Our findings suggest that activated NF-kappaB signaling contributes directly to malignant progression of ATL by preventing apoptosis, acting through the prosurvival protein survivin.
authors.affiliation: Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan.
authors.forename: Hirochika
authors.initials: H
authors.lastname: Kawakami
authors.forename: Mariko
authors.initials: M
authors.lastname: Tomita
authors.forename: Takehiro
authors.initials: T
authors.lastname: Matsuda
authors.forename: Takao
authors.initials: T
authors.lastname: Ohta
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujii
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hatano
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokuhisa
authors.forename: Naoki
authors.initials: N
authors.lastname: Mori
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D015973:Gene Expression Regulation, Leukemic; D016356:Gene Products, tax / Q000494:pharmacology*; D015368:Human T-lymphotropic virus 1; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007376:Interleukin-2 / Q000378:metabolism; D019169:Jurkat Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009363:Neoplasm Proteins; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D000077022:Survivin; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: C107489:BIRC5 protein, human; D016356:Gene Products, tax; D051034:Inhibitor of Apoptosis Proteins; D007376:Interleukin-2; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D000077022:Survivin