Department of Laboratory Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
Department of Laboratory Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
Anticancer Res. 2014 Jun;34(6):2913-8.
Signaling induced by binding of erythropoietin-producing hepatoma-amplified sequence (EPH) receptors to their cell-surface ephrin ligands is implicated in hematopoiesis and growth of various cancer cells. However, the roles of EPH-ephrin signaling in leukemia have not been elucidated. We investigated the effects of EPHB4 and ephrin B2 on the growth of leukemia cells.
Seven human leukemia cell lines were used to examine the effects of recombinant ephrin B2 and EPHB4 on cell proliferation by colorimetric WST-1 assay and colony assays; on protein tyrosine phosphorylation; and on mRNA expression by reverse transcription-polymerase chain reaction and microarray analysis.
In an erythroid leukemia-derived cell line AA, exogenous ephrin B2 induced proliferation and colony formation; in addition, it up-regulated protein tyrosine phosphorylation and the expression of growth-related genes such as FBJ murine osteosarcoma viral oncogene homolog B and v-src avian sarcoma viral oncogene homolog.
Growth-promoting effects of ephrin B2 were observed in an erythroid leukemia cell line, suggesting that the EPH-ephrin signaling may be involved in the pathology of leukemia.
促红细胞生成素产生肝细胞扩增序列（EPH）受体与其细胞表面的 Ephrin 配体结合所诱导的信号转导，与各种癌细胞的造血和生长有关。然而，EPH-ephrin 信号在白血病中的作用尚未阐明。我们研究了 EphB4 和 Ephrin B2 对白血病细胞生长的影响。
使用七种人白血病细胞系，通过比色 WST-1 测定法和集落测定法来检测重组 Ephrin B2 和 EphB4 对细胞增殖的影响；检测蛋白酪氨酸磷酸化；通过逆转录-聚合酶链反应和微阵列分析检测 mRNA 表达。
在红白血病衍生细胞系 AA 中，外源性 Ephrin B2 诱导增殖和集落形成；此外，它还上调了蛋白酪氨酸磷酸化和与生长相关的基因的表达，如 FBJ 鼠骨肉瘤病毒癌基因同源物 B 和 v-src 禽肉瘤病毒癌基因同源物。
在红白血病细胞系中观察到 Ephrin B2 的促生长作用，表明 EPH-ephrin 信号可能参与白血病的发病机制。
