The non-genotoxic activator of the p53 pathway Nutlin-3 shifts the balance between E2F7 and E2F1 transcription factors in leukemic cells.
The effect of Nutlin-3, a small molecule inhibitor of the MDM2/p53 interaction, was investigated on the steady-state mRNA levels of the transcription factors E2F1 and E2F7 in a cohort of primary B-chronic lymphocytic leukemia (B-CLL) patient samples (n = 15) and normal peripheral blood mononuclear cells (PBMC). A 24-h treatment with Nutlin-3 significantly down-regulated E2F1 and promoted the concomitant up-regulation of E2F7 in both leukemic and normal cells. Our data suggest that the ability of Nutlin-3 to up-regulate E2F7 likely represents an important molecular determinant in the anti-proliferative activity of Nutlin-3.
Department of Morphology and Embryology, University of Ferrara, Ferrara, Italy.
Maria Grazia
MG
di Iasio
Giorgio
G
Zauli
D016022:Case-Control Studies; D002478:Cells, Cultured; D050687:E2F1 Transcription Factor / Q000235:genetics*; D050702:E2F7 Transcription Factor / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007093:Imidazoles / Q000378:metabolism*; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D010879:Piperazines / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D050702:E2F7 Transcription Factor; C481054:E2F7 protein, human; D007093:Imidazoles; D010879:Piperazines; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C482205:nutlin 3