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Blood, 1 August 2006, Vol. 108, No. 3, pp. 1058-1064. Prepublished online as a Blood First Edition Paper on April 18, 2006; DOI 10.1182/blood-2005-08-007377. This Article Full Text (PDF) All Versions of this Article: blood-2005-08-007377v1 108/3/1058    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zhang, Q. Articles by Wasik, M. A Search for Related Content PubMed PubMed Citation Articles by Zhang, Q. Articles by Wasik, M. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 1, 2005 Accepted March 21, 2006 STAT3 induces transcription of DNA methyltransferase 1 (DNMT1) gene in malignant T-lymphocytes Qian Zhang, Hong Y Wang, Anders Woetmann, Puthiyaveettil N Raghunath, Niels Odum, and Mariusz A Wasik* Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA Department of Molecular Biology, University of Copenhagen, Copenhagen, Denmark * Corresponding author; email: wasik{at}mail.med.upenn.edu. In this study we demonstrate that STAT3, a well- characterized transcription factor expressed in continuously activated, oncogenic form in the large spectrum of cancer types, induces in malignant T lymphocytes expression of DNMT1, the key effector of epigenetic gene silencing. STAT3 binds in vitro to two STAT3 SIE/GAS binding sites identified in the promoter 1 and enhancer 1 of the DNMT1 gene. STAT3 also binds to the promoter 1 and enhancer 1 in vivo. Treatment of the malignant T lymphocytes with STAT3 siRNA abrogates expression of DNMT1, inhibits cell growth and induces programmed cell death. In turn, inhibition of DNMT1 by a small molecule inhibitor 5-aza-2-deoxy-cytidine and two different DNMT1 anti-sense DNA oligonucleotides, inhibits phosphorylation of STAT3 at the key tyrosine 705. These data indicate that STAT3 may in part transform cells by fostering epigenetic silencing of tumor suppressor genes. They also indicate that by inducing DNMT1, STAT3 facilitates its own persistent activation in the malignant T cells. Finally, these data provide further rationale for targeting therapeutically STAT3 in T-cell lymphomas and, possibly, other malignancies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Ambrogio, C. Martinengo, C. Voena, F. Tondat, L. Riera, P. F. di Celle, G. Inghirami, and R. Chiarle NPM-ALK Oncogenic Tyrosine Kinase Controls T-Cell Identity by Transcriptional Regulation and Epigenetic Silencing in Lymphoma Cells Cancer Res., November 15, 2009; 69(22): 8611 - 8619. [Abstract] [Full Text] [PDF] G. Lal and J. S. Bromberg Epigenetic mechanisms of regulation of Foxp3 expression Blood, October 29, 2009; 114(18): 3727 - 3735. [Abstract] [Full Text] [PDF] T. Krejsgaard, C. S. Vetter-Kauczok, A. Woetmann, H. Kneitz, K. W. Eriksen, P. Lovato, Q. Zhang, M. A. Wasik, C. Geisler, E. Ralfkiaer, et al. Ectopic expression of B-lymphoid kinase in cutaneous T-cell lymphoma Blood, June 4, 2009; 113(23): 5896 - 5904. [Abstract] [Full Text] [PDF] R. Hino, H. Uozaki, N. Murakami, T. Ushiku, A. Shinozaki, S. Ishikawa, T. Morikawa, T. Nakaya, T. Sakatani, K. Takada, et al. Activation of DNA Methyltransferase 1 by EBV Latent Membrane Protein 2A Leads to Promoter Hypermethylation of PTEN Gene in Gastric Carcinoma Cancer Res., April 1, 2009; 69(7): 2766 - 2774. [Abstract] [Full Text] [PDF] F. Rahnama, B. Thompson, M. Steiner, F. Shafiei, P. E. Lobie, and M. D. Mitchell Epigenetic Regulation of E-Cadherin Controls Endometrial Receptivity Endocrinology, March 1, 2009; 150(3): 1466 - 1472. [Abstract] [Full Text] [PDF] G. Lal, N. Zhang, W. van der Touw, Y. Ding, W. Ju, E. P. Bottinger, St. P. Reid, D. E. Levy, and J. S. Bromberg Epigenetic Regulation of Foxp3 Expression in Regulatory T Cells by DNA Methylation J. Immunol., January 1, 2009; 182(1): 259 - 273. [Abstract] [Full Text] [PDF] S. Garaud, C. Le Dantec, C. Berthou, P. M. Lydyard, P. Youinou, and Y. Renaudineau Selection of the Alternative Exon 1 from the cd5 Gene Down-Regulates Membrane Level of the Protein in B Lymphocytes J. Immunol., August 1, 2008; 181(3): 2010 - 2018. [Abstract] [Full Text] [PDF] M. Marzec, K. Halasa, M. Kasprzycka, M. Wysocka, X. Liu, J. W. Tobias, D. Baldwin, Q. Zhang, N. Odum, A. H. Rook, et al. Differential Effects of Interleukin-2 and Interleukin-15 versus Interleukin-21 on CD4+ Cutaneous T-Cell Lymphoma Cells Cancer Res., February 15, 2008; 68(4): 1083 - 1091. [Abstract] [Full Text] [PDF]

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