First Author | Shimabe M | Year | 2009 |
Journal | Oncogene | Volume | 28 |
Issue | 49 | Pages | 4364-74 |
PubMed ID | 19767769 | Mgi Jnum | J:156032 |
Mgi Id | MGI:4418594 | Doi | 10.1038/onc.2009.288 |
Citation | Shimabe M, et al. (2009) Pbx1 is a downstream target of Evi-1 in hematopoietic stem/progenitors and leukemic cells. Oncogene 28(49):4364-74 |
abstractText | Ecotropic viral integration site-1 (Evi-1) is a nuclear transcription factor, which is essential for the proliferation/maintenance of hematopoietic stem cells (HSCs). Aberrant expression of Evi-1 has been frequently found in myeloid leukemia, and is associated with a poor patient survival. Recently, we reported candidate target genes of Evi-1 shared in HSCs and leukemic cells using gene expression profiling analysis. In this study, we identified Pbx1, a proto-oncogene in hematopoietic malignancy, as a target gene of Evi-1. Overexpression of Evi-1 increased Pbx1 expression in hematopoietic stem/progenitor cells. An analysis of the Pbx1 promoter region revealed that Evi-1 upregulates Pbx1 transcription. Furthermore, reduction of Pbx1 levels through RNAi-mediated knockdown significantly inhibited Evi-1-induced transformation. In contrast, knockdown of Pbx1 did not impair bone marrow transformation by E2A/HLF or AML1/ETO, suggesting that Pbx1 is specifically required for the maintenance of bone marrow transformation mediated by Evi-1. These results indicate that Pbx1 is a target gene of Evi-1 involved in Evi-1-mediated leukemogenesis. |