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Blood, 15 May 2008, Vol. 111, No. 10, pp. 5118-5129. Prepublished online as a Blood First Edition Paper on February 27, 2008; DOI 10.1182/blood-2007-09-110635. This Article Full Text (PDF) Supplemental Methods, Tables, and Figures All Versions of this Article: blood-2007-09-110635v1 111/10/5118    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Saitoh, Y. Articles by Yamaoka, S. Search for Related Content PubMed PubMed Citation Articles by Saitoh, Y. Articles by Yamaoka, S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 10, 2007 Accepted February 17, 2008 Overexpressed NF-B inducing kinase contributes to the tumorigenesis of adult T-cell leukemia and Hodgkin Reed-Sternberg cells Yasunori Saitoh, Norio Yamamoto, MD. Zahidunnabi Dewan, Haruyo Sugimoto, Vicente J Martinez B, Yuki Iwasaki, Katsuyoshi Matsubara, Xiaohua Qi, Tatsuya Saitoh, Issei Imoto, Johji Inazawa, Atae Utsunomiya, Toshiki Watanabe, Takao Masuda, Naoki Yamamoto, and Shoji Yamaoka* Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan Department of host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Japan Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Japan Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan Department of Immunotherapeutics, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan * Corresponding author; email: shojmmb{at}tmd.ac.jp. The NF-B transcription factors play important roles in cancer development by preventing apoptosis and facilitating the tumor cell growth. However, the precise mechanisms by which NF-B is constitutively activated in specific cancer cells remain largely unknown. In our current study, we now report that NF-B inducing kinase (NIK) is overexpressed at the pre-translational level in adult T-cell leukemia (ATL) and Hodgkin Reed-Sternberg cells (H-RS) that do not express viral regulatory proteins. The overexpression of NIK causes cell transformation in rat fibroblasts, which is abolished by a super-repressor form of IB. Notably, depletion of NIK in ATL cells by RNA interference reduces the DNA-binding activity of NF-B and NF-B-dependent transcriptional activity, and efficiently suppresses tumor growth in NOD/SCID/cnull mice. These results indicate that the deregulated expression of NIK plays a critical role in constitutive NF-B activation in ATL and H-RS cells, and suggest also that NIK is an attractive molecular target for cancer therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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