|
|
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.
 Previous Article | Table of Contents | Next Article 
NEOPLASIA
Inducible activation of CEBPB, 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 Luisa Panno,
Ying Zhang,
Robert Martinez,
Danilo Perrotti, and
Bruno Calabretta
From the Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson Medical College, Philadelphia, PA; Department of Biomedical Sciences, Università di Modena e Reggio Emilia, Modena, Italy; Department of Cell Biology, Università degli Studi della Calabria, Calabria, Italy; Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics and the Comprehensive Cancer Center, Ohio State University, Columbus, OH; and Wyeth Genetics Institute, Cambridge, MA.
Translational regulation by oncogenic proteins may be a rapid and efficient mechanism to modulate gene expression. We report here the identification of the CEBPB gene as a target of translational regulation in myeloid precursor cells transformed by the BCR/ABL oncogene. Expression of CEBPB was repressed in 32D-BCR/ABL cells and reinduced by imatinib (STI571) via a mechanism that appears to depend on 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 CEBPB induced differentiation and inhibited proliferation of 32D-BCR/ABL cells in vitro and in mice, but a DNA binding-deficient CEBPB mutant had no effect. The proliferation-inhibitory effect of CEBPB was, in part, mediated by the CEBPB-induced GADD45A gene. Because expression of CEBPB (and CEBPA) is low in the 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:
|
|
|
|
 
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]
|
|
|
|
|
