Antisense RNA inhibition of phosphoprotein p18 expression abrogates the transformed phenotype of leukemic cells.
Antisense RNA inhibition of phosphoprotein p18 expression abrogates the transformed phenotype of leukemic cells.
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发表时间：
1996-03
期刊：
影响因子：
11.2
通讯作者：
S. Jeha;X. Luo;M. Beran;H. Kantarjian;G. Atweh
中科院分区：
文献类型：
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作者：
S. Jeha;X. Luo;M. Beran;H. Kantarjian;G. Atweh
磷蛋白p18最初是基于其在不同谱系的白血病细胞中的高水平表达而被鉴定的。与诱导白血病细胞分化相关的p18积聚和磷酸化水平的变化表明，这种磷酸蛋白在细胞增殖和分化中可能发挥作用，并可能在恶性转化中发挥作用。最近的研究表明，p18作为p34(Cdc2)激酶的底物，在细胞周期进程中发挥着重要作用。这些研究表明，抑制白血病细胞中p18的表达会导致细胞生长迟缓和G(2)-M期细胞积聚。本研究通过研究抑制p18表达对K562红白血病细胞恶性表型的影响，探讨p18在细胞转化中的作用。这些研究表明，反义抑制白血病细胞中p18的表达会导致较低饱和密度下的生长停滞，失去血清独立性，并失去体外锚定非依赖性生长。此外，在严重联合免疫缺陷小鼠模型中，抑制p18的表达会显著抑制白血病细胞在体内的致瘤性。这些研究表明，白血病细胞中p18的高水平表达是维持转化表型所必需的，并提示p18是抗白血病干预的潜在靶点。
Phosphoprotein p18 was identified originally on the basis of its very high level of expression in leukemic cells of different lineages. Changes in the level of p18 accumulation and phosphorylation associated with induction of differentiation 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 p18 plays an important role in cell cycle progression by serving as a substrate for p34(cdc2) kinase. These studies showed that inhibition of p18 expression in leukemic cells results in growth retardation and accumulation of cells in G(2)-M. In this study, we explore the potential role of p18 in cellular transformation by investigating the effects of inhibition of p18 expression on the malignant phenotype of K562 erythroleukemia cells. These studies show that antisense inhibition of p18 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 p18 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 p18 expression in leukemic cells is necessary for the maintenance of the transformed phenotype and suggest p18 as a potential target for antileukemic interventions.