SEARCH:   Advanced

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 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 Citation Map 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 HighWire 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. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Overexpressed NF-B–inducing kinase contributes to the tumorigenesis of adult T-cell leukemia and Hodgkin Reed-Sternberg cells Yasunori Saitoh1, Norio Yamamoto1, M. Zahidunnabi Dewan1, Haruyo Sugimoto1, Vicente J. Martinez Bruyn1, Yuki Iwasaki1, Katsuyoshi Matsubara1, Xiaohua Qi1, Tatsuya Saitoh2, Issei Imoto3, Johji Inazawa3, Atae Utsunomiya4, Toshiki Watanabe5, Takao Masuda6, Naoki Yamamoto1,7, and Shoji Yamaoka1 1 Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo; 2 Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita; 3 Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo; 4 Department of Hematology, Imamura Bun-in Hospital, Kagoshima; 5 Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo; 6 Department of Immunotherapeutics, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo; and 7 AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan The nuclear factor-B (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 pretranslational 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? This article has been cited by other articles: T. Zhao, J.-i. Yasunaga, Y. Satou, M. Nakao, M. Takahashi, M. Fujii, and M. Matsuoka Human T-cell leukemia virus type 1 bZIP factor selectively suppresses the classical pathway of NF-{kappa}B Blood, March 19, 2009; 113(12): 2755 - 2764. [Abstract] [Full Text] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020