FUNCTION OF ECOTROPIC VIRAL INTEGRATION SITE 1 (EVI1) GENE IN MOUSE NEURAL PRECURSOR CELLS AND HUMAN GLIOMA INITIATING CELLS

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Abstract

BACKGROUND: Ecotropic viral integration site 1 (EVI1) gene encodes a transcription factor, containing ten zinc finger motifs found within two domains of the protein. Abnormal expression of EVI1 is found in 5-10% of patients with acute myeloid leukemia (AML), and is associated with unfavorable outcome. EVI1 maintains the self-renewal capacity of hematopoietic stem cells (HSCs), of cell quiescence and stem cell-like phenotypes in leukemia cells. EVI1 knocked out mice die approximately 10.5 days post-coitus (d.p.c.; E10.5) with defect or hypoplasty in heart, cranial ganglia, peripheral nervous system. It is possible that EVI1 also regulates the fate of neural stem cells (NPCs) and glioma initiating cells (GICs) as well as HSCs. METHODS: We investigated the biological effect of knockdown and overexpression of EVI1 against NPCs and GICs. RESULTS: We found that NPCs from nestin-cre induced EVI1 (-/-) mouse differentiated to neuron and glial cells earlier than wild type NPCs. Notch signals were altered in EVI1 (-/-) NPCs. Knockdown experiment with shEVI1 in GICs showed the monolayerd GICs hard to stick to laminin-coated dish by alteration of integrin signals. Because laminin is a major component of niche of NPCs and GICs, EVI1 has an important role to maintain the stem cell capacity by committing to niche. Moreover overexpression of EVI1 in U87 MG and GICs decreased cell proliferation. CONCLUSIONS: Taken together, EVI1 regulates the cell fate and proliferation of NPCs and GICs. SECONDARY CATEGORY: n/a.

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