Overexpression of Aurora A by loss of CHFR gene expression increases the growth and survival of HTLV-1-infected T cells through enhanced NF-κB activity

Mariko Tomita, Minoru Toyota, Chie Ishikawa, Tetsuro Nakazato, Taeko Okudaira, Takehiro Matsuda, Jun Nosuke Uchihara, Naoya Taira, Kazuiku Ohshiro, Masachika Senba, Yuetsu Tanaka, Koichi Ohshima, Hideyuki Saya, Takashi Tokino, Naoki Mori

Research output: Contribution to journalArticle

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Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent for adult T-cell leukemia (ATL). Aurora A, a mitotic checkpoint protein, is overexpressed in human cancer cells. The cell cycle-dependent turnover of Aurora A is regulated by E3 ubiquitin ligases such as checkpoint with fork head-associated and ring finger (CHFR). Here, we found overexpression of Aurora A protein in HTLV-1-infected T-cell lines and primary ATL cells. The expression of CHFR mRNA was reduced in these cells by abnormal methylation of CHFR promoter region. Knockdown of Aurora A using small interfering RNA suppressed the growth of HTLV-1-infected T-cell line. Transfection of Aurora A expression plasmid enhanced Tax-induced nuclear factor-κB (NF-κB) reporter activity. Transfection of CHFR expression plasmid into an HTLV-1-infected T-cell line reduced cell growth, Aurora A protein level and constitutive NF-κB reporter activity. Aurora kinase inhibitor suppressed the growth and survival of HTLV-1-infected T-cell lines and primary ATL cells. It also reduced constitutive NF-κB activity in an HTLV-1-infected T-cell line by reducing IκB kinase κ phosphorylation and the expression of antiapoptotic protein survivin. Our results suggested that loss of CHFR expression resulted to accumulation of Aurora A, which increased NF-κB activity. These findings highlight the critical role of Aurora A in HTLV-1-infected T cells, making this molecule a potentially suitable target for future therapies for ATL.

Original languageEnglish
Pages (from-to)2607-2615
Number of pages9
JournalInternational Journal of Cancer
Volume124
Issue number11
DOIs
Publication statusPublished - 2009 Jun 1

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Deltaretrovirus
Adult T Cell Leukemia Lymphoma
T-Lymphocytes
Gene Expression
Survival
Growth
Cell Line
Transfection
Proteins
Plasmids
Aurora Kinases
M Phase Cell Cycle Checkpoints
Growth Inhibitors
Ubiquitin-Protein Ligases
Genetic Promoter Regions
Methylation
Small Interfering RNA
Fingers
Cell Cycle
Phosphotransferases

Keywords

  • ATL
  • Aurora A
  • Aurora kinase inhibitor
  • CHFR
  • HTLV-1

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Overexpression of Aurora A by loss of CHFR gene expression increases the growth and survival of HTLV-1-infected T cells through enhanced NF-κB activity. / Tomita, Mariko; Toyota, Minoru; Ishikawa, Chie; Nakazato, Tetsuro; Okudaira, Taeko; Matsuda, Takehiro; Uchihara, Jun Nosuke; Taira, Naoya; Ohshiro, Kazuiku; Senba, Masachika; Tanaka, Yuetsu; Ohshima, Koichi; Saya, Hideyuki; Tokino, Takashi; Mori, Naoki.

In: International Journal of Cancer, Vol. 124, No. 11, 01.06.2009, p. 2607-2615.

Research output: Contribution to journalArticle

Tomita, M, Toyota, M, Ishikawa, C, Nakazato, T, Okudaira, T, Matsuda, T, Uchihara, JN, Taira, N, Ohshiro, K, Senba, M, Tanaka, Y, Ohshima, K, Saya, H, Tokino, T & Mori, N 2009, 'Overexpression of Aurora A by loss of CHFR gene expression increases the growth and survival of HTLV-1-infected T cells through enhanced NF-κB activity', International Journal of Cancer, vol. 124, no. 11, pp. 2607-2615. https://doi.org/10.1002/ijc.24257
Tomita, Mariko ; Toyota, Minoru ; Ishikawa, Chie ; Nakazato, Tetsuro ; Okudaira, Taeko ; Matsuda, Takehiro ; Uchihara, Jun Nosuke ; Taira, Naoya ; Ohshiro, Kazuiku ; Senba, Masachika ; Tanaka, Yuetsu ; Ohshima, Koichi ; Saya, Hideyuki ; Tokino, Takashi ; Mori, Naoki. / Overexpression of Aurora A by loss of CHFR gene expression increases the growth and survival of HTLV-1-infected T cells through enhanced NF-κB activity. In: International Journal of Cancer. 2009 ; Vol. 124, No. 11. pp. 2607-2615.
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AU - Senba, Masachika

AU - Tanaka, Yuetsu

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