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Blood, 15 March 2007, Vol. 109, No. 6, pp. 2496-2504. Prepublished online as a Blood First Edition Paper on December 5, 2006; DOI 10.1182/blood-2006-07-034231. This Article Full Text (PDF) All Versions of this Article: blood-2006-07-034231v1 109/6/2496    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 Conti, L. Articles by Novelli, F. Search for Related Content PubMed PubMed Citation Articles by Conti, L. Articles by Novelli, F. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 7, 2006 Accepted October 31, 2006 In the absence of IGF-1 signaling, IFN- suppresses human malignant T cell growth Laura Conti, Gabriella Regis, Angela Longo, Paola Bernabei, Roberto Chiarle, Mirella Giovarelli, and Francesco Novelli* Center for Experimental Research & Medical Studies (CERMS), San Giovanni Battista Hospital, Turin, Italy Dept of Medicine & Experimental Oncology, Section of Pathology, University of Turin, Turin, Italy * Corresponding author; email: franco.novelli{at}unito.it. Several approaches to target Insulin-like Growth Factor (IGF)-1 signaling have resulted in the inhibition of the growth of a broad range of tumor cells. Malignant T cells are insensitive to the antiproliferative effects of the Interferon (IFN)-/Signal Transducer and Activator of Transcription (STAT) 1 pathway because of the IGF-1-dependent internalization of the IFN-R2 signaling chain. Here we show that human malignant T cells are also resistant to the growth inhibitory effect of both the IGF-1 receptor specific inhibitor picropodophyllin (PPP) and retrovirus-mediated gene transfer of a dominant negative IGF-1 receptor. However, blockade of IGF-1 receptor perturbs IFN-R2 internalization and induces its cell surface accumulation in malignant T cells. This allows the reinstatement of the IFN--induced STAT1 activation, a high expression of pro-apoptotic molecules and the suppression of malignant T cell growth both in vitro and in vivo in a SCID mouse model. These data indicate that the inhibition of IGF-1 signaling combined with IFN- administration could be a promising approach to suppress the growth of neoplastic T cells resistant to each treatment on its own. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Vasilcanu, D. Vasilcanu, B. Sehat, S. Yin, A. Girnita, M. Axelson, and L. Girnita Insulin-Like Growth Factor Type-I Receptor-Dependent Phosphorylation of Extracellular Signal-Regulated Kinase 1/2 but not Akt (Protein Kinase B) Can Be Induced by Picropodophyllin Mol. Pharmacol., March 1, 2008; 73(3): 930 - 939. [Abstract] [Full Text] [PDF]

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