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Blood, 1 September 2008, Vol. 112, No. 5, pp. 1942-1950. Prepublished online as a Blood First Edition Paper on June 12, 2008; DOI 10.1182/blood-2007-09-114975. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2007-09-114975v1 112/5/1942    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Soliera, A. R. Articles by Calabretta, B. Search for Related Content PubMed PubMed Citation Articles by Soliera, A. R. Articles by Calabretta, B. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Transcriptional repression of c-Myb and GATA-2 is involved in the biologic effects of C/EBP in p210BCR/ABL-expressing cells Angela Rachele Soliera1, Maria Rosa Lidonnici1, Giovanna Ferrari-Amorotti2, Marco Prisco1, Ying Zhang3, Robert V. Martinez3, Nick J. Donato4, and Bruno Calabretta1 1 Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson Medical College, Philadelphia, PA; 2 Department of Biomedical Sciences, University of Modena Medical School, Modena, Italy; 3 Department of Biological Technologies, Wyeth Research, Cambridge, MA; and 4 Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor Ectopic C/EBP expression in p210BCR/ABL-expressing hematopoietic cells induces granulocytic differentiation, inhibits proliferation, and suppresses leukemogenesis. To assess the underlying mechanisms, C/EBP targets were identified by microarray analyses. Upon C/EBP activation, expression of c-Myb and GATA-2 was repressed in 32D-BCR/ABL, K562, and chronic myelogenous leukemia (CML) blast crisis (BC) primary cells but only c-Myb levels decreased slightly in CD34+ normal progenitors. The role of these 2 genes for the effects of C/EBP was assessed by perturbing their expression in K562 cells. Ectopic c-Myb expression blocked the proliferation inhibition– and differentiation-inducing effects of C/EBP, whereas c-Myb siRNA treatment enhanced C/EBP-mediated proliferation inhibition and induced changes in gene expression indicative of monocytic differentiation. Ectopic GATA-2 expression suppressed the proliferation inhibitory effect of C/EBP but blocked in part the effect on differentiation; GATA-2 siRNA treatment had no effects on C/EBP induction of differentiation but inhibited proliferation of K562 cells, alone or upon C/EBP activation. In summary, the effects of C/EBP in p210BCR/ABL-expressing cells depend, in part, on transcriptional repression of c-Myb and GATA-2. Since perturbation of c-Myb and GATA-2 expression has nonidentical consequences for proliferation and differentiation of K562 cells, the effects of C/EBP appear to involve dif-ferent transcription-regulated targets. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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