Antisense RNA Inhibition of Phosphoprotein pl8 Expression Abrogates the Transformed Phenotype of Leukemic Cells1
نویسندگان
چکیده
Phosphoprotcin plS was identified originally on the basis of its ven high level of expression in leukemic cells of different lineages. Changes in the level of plK accumulation and phosphorylation associated with induction of dif ferentiation of leukemic cells suggested a potential role for this phosphoprotein in cellular proliferation and differentiation and possibly in malignant transformation. Recent studies have demonstrated that plS plays an impor tant role in cell cycle progression by serving as a substrate for p34"k2 kinase. These studies showed that inhibition of p IX expression in leukemic cells results in growth retardation and accumulation of cells in (. .-M. In this study, we explore the potential role of pl8 in cellular transformation by investigating the effects of inhibition of plS expression on the malignant phenotype of K562 erythroleukemia cells. These studies show that antisense inhibition of pl8 expression in leukemic cells results in growth arrest at a lower saturation density, loss of serum independence, and loss of anchorage-independent growth in vitro. In addition, inhibition of pl8 expression results in a marked inhibition of tumorigenicity of leukemic cells in vivo in the severe combined immune deficiency mouse model. These studies demonstrate that the high level of |iIS expression in leukemic cells is necessary for the maintenance of the transformed phenotype and suggest pI8 as a potential target for antileukemic interventions.
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