Effects of C/EBPalpha and C/EBPbeta in BCR/ABL-Expressing Cells: Differences and Similarities.

Posted by rob on June 19, 2006 under Uncategorized | Be the First to Comment

Guerzoni C, Ferrari-Amorotti G, Bardini M, Mariani SA, Calabretta B.

Department of Biomedical Sciences, Universita di Modena e Reggio Emilia, Modena, Italy.

C/EBPalpha and C/EBPbeta, two transcription factors of the C/EBP family play important roles in the proliferation and differentiation of various cell types including myeloid progenitors. Expression of C/EBPalpha and C/EBPbeta is repressed in myeloid blast crisis of Chronic Myelogenous Leukemia by mechanisms that involve translation repression which depends on the interaction of RNA-binding proteins with conserved binding sites in the 5′UTR of c/ebpalpha and c/ebpbeta mRNA. Ectopic expression of C/EBPalpha and C/EBPbeta in myeloid progenitors expressing the BCR/ABL oncogene inhibits proliferation, induces differentiation and suppresses leukemogenesis in mice, but C/EBPalpha is markedly more effective than C/EBPbeta. The more potent effects of C/EBPalpha probably depends on protein-protein interaction with cell-cycle regulatory proteins, but the pattern of genes modulated by C/EBPalpha and C/EBPbeta is not completely overlapping. This suggests that transcription-dependent and -independent effects are both involved and support the therapeutic potential of reactivating C/EBPalpha and C/EBPbeta expression in leukemic cells.

PMID: 16760662 [PubMed - as supplied by publisher]

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