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, Bruno Calabretta

Research output: Contribution to journalArticle

Abstract

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/ebpβ mRNA. Constitutive expression or conditional activation of wildtype 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.

Original languageEnglish
Pages (from-to)4080-4089
Number of pages10
JournalBlood
Volume107
Issue number10
DOIs
Publication statusPublished - May 15 2006

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Blast Crisis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Genes
Chemical activation
Intergenic DNA
RNA-Binding Proteins
Myeloid Cells
Oncogenes
Gene expression
Protein-Tyrosine Kinases
Leukemia
Gene Expression
Messenger RNA
DNA
Proteins
Imatinib Mesylate
Therapeutics
In Vitro Techniques

ASJC Scopus subject areas

  • Hematology

Cite this

Guerzoni, C., Bardini, M., Mariani, S. A., Ferrari-Amorotti, G., Neviani, P., Panno, M. L., ... Calabretta, B. (2006). Inducible activation of CEBPB, a gene negatively regulated by BCR/ABL, inhibits proliferation and promotes differentiation of BCR/ABL-expressing cells. Blood, 107(10), 4080-4089. https://doi.org/10.1182/blood-2005-08-3181

Inducible activation of CEBPB, a gene negatively regulated by BCR/ABL, inhibits proliferation and promotes differentiation of BCR/ABL-expressing cells. / Guerzoni, Clara; Bardini, Michela; Mariani, Samanta A.; Ferrari-Amorotti, Giovanna; Neviani, Paolo; Panno, Maria Luisa; Zhang, Ying; Martinez, Robert; Perrotti, Danilo; Calabretta, Bruno.

In: Blood, Vol. 107, No. 10, 15.05.2006, p. 4080-4089.

Research output: Contribution to journalArticle

Guerzoni, C, Bardini, M, Mariani, SA, Ferrari-Amorotti, G, Neviani, P, Panno, ML, Zhang, Y, Martinez, R, Perrotti, D & Calabretta, B 2006, 'Inducible activation of CEBPB, a gene negatively regulated by BCR/ABL, inhibits proliferation and promotes differentiation of BCR/ABL-expressing cells', Blood, vol. 107, no. 10, pp. 4080-4089. https://doi.org/10.1182/blood-2005-08-3181
Guerzoni, Clara ; Bardini, Michela ; Mariani, Samanta A. ; Ferrari-Amorotti, Giovanna ; Neviani, Paolo ; Panno, Maria Luisa ; Zhang, Ying ; Martinez, Robert ; Perrotti, Danilo ; Calabretta, Bruno. / Inducible activation of CEBPB, a gene negatively regulated by BCR/ABL, inhibits proliferation and promotes differentiation of BCR/ABL-expressing cells. In: Blood. 2006 ; Vol. 107, No. 10. pp. 4080-4089.
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