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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 (PDF) Supplemental Figures Erratum (v114,p1720) 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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 28, 2007 Accepted June 7, 2008 Oncogenic Kit controls neoplastic mast cell growth through a Stat5/PI 3-kinase signaling cascade Noria Harir, Cedric Boudot, Katrin Friedbichler, Karoline Sonneck, Rudin Kondo, Severine Martin-Lanneree, Lukas Kenner, Marc Kerenyi, Saliha Yahiaoui, Valerie Gouilleux-Gruart, Jean Gondry, Laurence Benit, Isabelle Dusanter-Fourt, Kaiss Lassoued, Peter Valent, Richard Moriggl, and Fabrice Gouilleux* INSERM E351, Universite de Picardie J Vernes, Amiens, France Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria Department of Internal Medicine I, Division of Hematology, Medical University of Vienna, Vienna, Austria Institut Cochin, Universite Paris Descartes, Paris, France Department of Pathology, Medical University of Vienna, Vienna, Austria Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University of Vienna, Vienna, Austria Centre Gynecologie-Obstetrique, Centre Hospitalier Universitaire, Amiens, France INSERM, U567, Paris, France * Corresponding author; email: fabrice.gouilleux{at}sa.u-picardie.fr. 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 MC. Primary neoplastic Kit D816V+ MC 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+ MC. These data suggest that a downstream Stat5-PI3K-Akt signaling-cascade is essential for Kit D816V-mediated growth and survival of neoplastic MC. 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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