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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3200-3205. Prepublished online as a Blood First Edition Paper on July 14, 2005; DOI 10.1182/blood-2005-04-1386. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-04-1386v1 106/9/3200    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 Beyne-Rauzy, O. Articles by Mansat-De Mas, V. Search for Related Content PubMed PubMed Citation Articles by Beyne-Rauzy, O. Articles by Mansat-De Mas, V. Related Collections Neoplasia Signal Transduction Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Tumor necrosis factor- inhibits hTERT gene expression in human myeloid normal and leukemic cells Odile Beyne-Rauzy, Naïs Prade-Houdellier, Cécile Demur, Christian Recher, Jacques Ayel, Guy Laurent, and Véronique Mansat-De Mas From the Institut National de la Santé et de la Recherche Médicale (INSERM) U563, Centre Hospitalier et Universitaire (CHU) Purpan, Toulouse, France; the Service de Médecine Interne, CHU Purpan, Toulouse, France; the Laboratoire d'Hématologie Biologique, CHU Purpan, Toulouse, France; the Service d'Hématologie, CHU Purpan, Toulouse, France; and the Service d'Orthopédie, CHU Purpan, Toulouse, France. Telomerase catalytic subunit (hTERT) has been shown to play a critical role not only in telomere homeostasis but also in cellular survival, DNA repair, and genetic stability. In a previous study, we described that tumor necrosis factor-x (TNFx) induced in the leukemic KG1 cells a senescence state characterized by decreased hTERT activity followed by prolonged growth arrest, increasedx -galactosidase activity, telomere shortening, and major chromosomal instability. Interestingly, granulocyte-macrophage colony-stimulating factor (GM-CSF) abrogated all these events. In the present study, we show for the first time that TNFx acts by inhibiting the hTERT gene in both normal CD34x+ cells and fresh leukemic cells. Using KG1 cells as a representative cellular model, we show that TNFx induced sphingomyelin hydrolysis, ceramide production, and c-Jun N-terminal kinase (JNK) activation, all of which are critical components of TNFx signaling, resulting in hTERT gene inhibition. Moreover, we provide evidence that the protective effect of GM-CSF is related to its capacity to interfere with both ceramide generation and ceramide signaling. Negative regulation of the hTERT gene may represent one mechanism by which TNFx interferes with normal hemopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. G. Wooten-Blanks, P. Song, C. E. Senkal, and B. Ogretmen Mechanisms of ceramide-mediated repression of the human telomerase reverse transcriptase promoter via deacetylation of Sp3 by histone deacetylase 1 FASEB J, October 1, 2007; 21(12): 3386 - 3397. [Abstract] [Full Text] [PDF] A. K. Damjanovic, Y. Yang, R. Glaser, J. K. Kiecolt-Glaser, H. Nguyen, B. Laskowski, Y. Zou, D. Q. Beversdorf, and N.-p. Weng Accelerated Telomere Erosion Is Associated with a Declining Immune Function of Caregivers of Alzheimer's Disease Patients J. Immunol., September 15, 2007; 179(6): 4249 - 4254. [Abstract] [Full Text] [PDF]

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