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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2463-2473. Prepublished online as a Blood First Edition Paper on June 25, 2008; DOI 10.1182/blood-2007-09-115477. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-09-115477v1 112/6/2463    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 Harir, N. Articles by Gouilleux, F. Search for Related Content PubMed PubMed Citation Articles by Harir, N. Articles by Gouilleux, F. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Oncogenic Kit controls neoplastic mast cell growth through a Stat5/PI3-kinase signaling cascade Noria Harir1,*, Cédric Boudot1,*, Katrin Friedbichler2, Karoline Sonneck3, Rudin Kondo3, Séverine Martin-Lannerée4,5, Lukas Kenner2,6, Marc Kerenyi7, Saliha Yahiaoui1, Valérie Gouilleux-Gruart1, Jean Gondry8, Laurence Bénit4,5, Isabelle Dusanter-Fourt4,5, Kaïss Lassoued1, Peter Valent3, Richard Moriggl2,, and Fabrice Gouilleux1, 1 Inserm (EMI 351), Faculté de Médecine, Université de Picardie J. Verne, Amiens, France; 2 Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria; 3 Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Austria; 4 Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France; 5 Inserm U567, Paris, France; 6 Department of Pathology, Medical University of Vienna, Austria; 7 Max F. Perutz Laboratories, Department of Medical Biochemistry, Division of Molecular Biology, Medical University of Vienna, Austria; and 8 Centre Gynécologie-Obstétrique, Centre Hospitalier Universitaire, Amiens, France The D816V-mutated variant of Kit triggers multiple signaling pathways and is considered essential for malignant transformation in mast cell (MC) neoplasms. We here describe that constitutive activation of the Stat5-PI3K-Akt-cascade controls neoplastic MC development. Retrovirally transduced active Stat5 (cS5F) was found to trigger PI3K and Akt activation, and to transform murine bone marrow progenitors into tissue-infiltrating MCs. Primary neoplastic Kit D816V+ MCs in patients with mastocytosis also displayed activated Stat5, which was found to localize to the cytoplasm and to form a signaling complex with PI3K, with consecutive Akt activation. Finally, the knock-down of either Stat5 or Akt activity resulted in growth inhibition of neoplastic Kit D816V+ MCs. These data suggest that a downstream Stat5-PI3K-Akt signaling cascade is essential for Kit D816V-mediated growth and survival of neoplastic MCs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. M. Vannucchi, P. Guglielmelli, and A. Tefferi Advances in Understanding and Management of Myeloproliferative Neoplasms CA Cancer J Clin, May 1, 2009; 59(3): 171 - 191. [Abstract] [Full Text] [PDF] H. Neuwirt, M. Puhr, F. R. Santer, M. Susani, W. Doppler, G. Marcias, V. Rauch, M. Brugger, A. Hobisch, L. Kenner, et al. Suppressor of Cytokine Signaling (SOCS)-1 Is Expressed in Human Prostate Cancer and Exerts Growth-Inhibitory Function through Down-Regulation of Cyclins and Cyclin-Dependent Kinases Am. J. Pathol., May 1, 2009; 174(5): 1921 - 1930. [Abstract] [Full Text] [PDF]

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