| Literature DB >> 17097562 |
Karen Keeshan1, Yiping He, Bas J Wouters, Olga Shestova, Lanwei Xu, Hong Sai, Carlos G Rodriguez, Ivan Maillard, John W Tobias, Peter Valk, Martin Carroll, Jon C Aster, Ruud Delwel, Warren S Pear.
Abstract
Tribbles homolog 2 (Trib2) was identified as a downregulated transcript in leukemic cells undergoing growth arrest. To investigate the effects of Trib2 in hematopoietic progenitors, mice were reconstituted with hematopoietic stem cells retrovirally expressing Trib2. Trib2-transduced bone marrow cells exhibited a growth advantage ex vivo and readily established factor-dependent cell lines. In vivo, Trib2-reconstituted mice uniformly developed fatal transplantable acute myelogenous leukemia (AML). In mechanistic studies, we found that Trib2 associated with and inhibited C/EBPalpha. Furthermore, Trib2 expression was elevated in a subset of human AML patient samples. Together, our data identify Trib2 as an oncogene that induces AML through a mechanism involving inactivation of C/EBPalpha.Entities:
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Year: 2006 PMID： 17097562 PMCID： PMC2839500 DOI： 10.1016/j.ccr.2006.09.012
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743