SEARCH:   Advanced

Blood, 15 May 2006, Vol. 107, No. 10, pp. 4080-4089. Prepublished online as a Blood First Edition Paper on January 17, 2006; DOI 10.1182/blood-2005-08-3181. This Article Full Text (PDF) All Versions of this Article: 2005-08-3181v1 107/10/4080    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 Guerzoni, C. Articles by Calabretta, B. Search for Related Content PubMed PubMed Citation Articles by Guerzoni, C. Articles by Calabretta, B. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 10, 2005 Accepted January 7, 2006 Inducible activation of C/EBP, a gene negatively regulated by BCR/ABL, inhibits proliferation and promotes differentiation of BCR/ABL-expressing cells Clara Guerzoni, Michela Bardini, Samanta A Mariani, Giovanna Ferrari-Amorotti, Paolo Neviani, Maria L Panno, Ying Zhang, Robert Martinez, Danilo Perrotti, and Bruno Calabretta* Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson Medical College, Philadelphia, PA, USA; Department of Biomedical Sciences, Universita di Modena e Reggio Emilia, Modena, Italy Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson Medical College, Philadelphia, PA, USA Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics and the Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA Department of Cell Biology, Universita degli Studi della Calabria, Cosenza, Italy Wyeth Genetics Institute, Cambridge, MA, USA * Corresponding author; email: b_calabretta{at}mail.jci.tju.edu. Translational regulation by oncogenic proteins may be a rapid and efficient mechanism to modulate gene expression. We report here the identification of the C/EBP gene as a target of translational regulation in myeloid precursor cells transformed by the BCR/ABL oncogene. Expression of C/EBP was repressed in 32D-BCR/ABL cells and reinduced by STI571 via a mechanism requiring expression of the CUG-repeat RNA binding protein CUGBP1 and the integrity of the CUG-rich intercistronic region of c/ebp mRNA. Constitutive expression or conditional activation of wild-type C/EBP induced differentiation and inhibited proliferation of 32D-BCR/ABL cells in vitro and in mice, but a DNA-binding deficient C/EBP mutant had no effect. The proliferation-inhibitory effect of C/EBP was, in part, mediated by the C/EBP- induced GADD45 gene. Since expression of C/EBP (and C/EBP) is low in the aggressive blast crisis (BC) stage of chronic myelogenous leukemia (CML) and is inversely correlated with BCR/ABL tyrosine kinase levels, these findings point to the therapeutic potential of restoring C/EBP activity in CML-BC and, perhaps, other types of acute leukemia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Costinean, S. K. Sandhu, I. M. Pedersen, E. Tili, R. Trotta, D. Perrotti, D. Ciarlariello, P. Neviani, J. Harb, L. R. Kauffman, et al. Src homology 2 domain-containing inositol-5-phosphatase and CCAAT enhancer-binding protein {beta} are targeted by miR-155 in B cells of E{micro}-MiR-155 transgenic mice Blood, August 13, 2009; 114(7): 1374 - 1382. [Abstract] [Full Text] [PDF] Y. Gao, A. Howard, K. Ban, and J. Chandra Oxidative Stress Promotes Transcriptional Up-regulation of Fyn in BCR-ABL1-expressing Cells J. Biol. Chem., March 13, 2009; 284(11): 7114 - 7125. [Abstract] [Full Text] [PDF] A. M. Eiring, P. Neviani, R. Santhanam, J. J. Oaks, J. S. Chang, M. Notari, W. Willis, C. Gambacorti-Passerini, S. Volinia, G. Marcucci, et al. Identification of novel posttranscriptional targets of the BCR/ABL oncoprotein by ribonomics: requirement of E2F3 for BCR/ABL leukemogenesis Blood, January 15, 2008; 111(2): 816 - 828. [Abstract] [Full Text] [PDF] J. S. Chang, R. Santhanam, R. Trotta, P. Neviani, A. M. Eiring, E. Briercheck, M. Ronchetti, D. C. Roy, B. Calabretta, M. A. Caligiuri, et al. High levels of the BCR/ABL oncoprotein are required for the MAPK-hnRNP-E2 dependent suppression of C/EBP{alpha}-driven myeloid differentiation Blood, August 1, 2007; 110(3): 994 - 1003. [Abstract] [Full Text] [PDF] S. Chu, L. Li, H. Singh, and R. Bhatia BCR-Tyrosine 177 Plays an Essential Role in Ras and Akt Activation and in Human Hematopoietic Progenitor Transformation in Chronic Myelogenous Leukemia Cancer Res., July 15, 2007; 67(14): 7045 - 7053. [Abstract] [Full Text] [PDF] T. Akasaka, T. Balasas, L. J. Russell, K.-j. Sugimoto, A. Majid, R. Walewska, E. L. Karran, D. G. Brown, K. Cain, L. Harder, et al. Five members of the CEBP transcription factor family are targeted by recurrent IGH translocations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) Blood, April 15, 2007; 109(8): 3451 - 3461. [Abstract] [Full Text] [PDF] D. Perrotti and P. Neviani From mRNA Metabolism to Cancer Therapy: Chronic Myelogenous Leukemia Shows the Way Clin. Cancer Res., March 15, 2007; 13(6): 1638 - 1642. [Abstract] [Full Text] [PDF] G. Ferrari-Amorotti, K. Keeshan, M. Zattoni, C. Guerzoni, G. Iotti, S. Cattelani, N. J. Donato, and B. Calabretta Leukemogenesis induced by wild-type and STI571-resistant BCR/ABL is potently suppressed by C/EBP{alpha} Blood, August 15, 2006; 108(4): 1353 - 1362. [Abstract] [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020