Expression and Role of the ErbB3-Binding Protein 1 in Acute Myelogenous Leukemic Cells

L. X. T. Nguyen, L. Zhu, Y. Lee, L. Ta, B. S. Mitchell
2016 Clinical Cancer Research  
Purpose: The ErbB3-binding protein 1 (Ebp1) has been implicated in diverse cancers as having either oncogenic or tumor suppressor activities. The present study was undertaken to determine the effects of Ebp1 expression in AML cells and to determine the mechanisms by which Ebp1 promotes cell proliferation in these cells. Experimental Design: The expression of Ebp1 was studied in mononuclear cells obtained from the peripheral blood of 54 patients with AML by Western blot analysis. The effects of
more » ... bp1 expression on proliferating cell nuclear antigen (PCNA) expression and cell proliferation was measured using Western blot analysis, immunoprecipitation, in vitro ubiquitination, and colony-forming assays. The role of Ebp1 in promoting rRNA synthesis and cell proliferation was evaluated by measuring the level of pre-rRNA and the recruitment of Pol I to rDNA. Results: Ebp1 is highly expressed in acute myelogenous leukemia (AML) cells and regulates the level of ribosomal RNA (rRNA) synthesis by binding to RNA Polymerase I (Pol I) and enhancing the formation of the Pol I initiation complex. Ebp1 also increases the stability of PCNA protein by preventing its interaction with Mdm2, for which it is a substrate. Conclusions: These results demonstrate an important role of Ebp1 in promoting cell proliferation in AML cells through the regulation of both rRNA synthesis and PCNA expression. Clin Cancer Res; 22(13); 3320-7. Ó2016 AACR. Materials and Methods Human patient samples Mononuclear cells were isolated from the bone marrow or
doi:10.1158/1078-0432.ccr-15-2282 pmid:26813358 fatcat:gvzx5ytn75ar7cwtg7fxddknfe