Activation of c-kit by stem cell factor induces radioresistance to apoptosis through ERK-dependent expression of survivin in HL60 cells
Activation of c-kit by stem cell factor induces radioresistance to apoptosis through ERK-dependent expression of survivin in HL60 cells
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DOI：
10.1269/jrr.45.557
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发表时间：
2004-12-01
影响因子：
2
通讯作者：
Kuwabara, M
中科院分区：
文献类型：
--
作者：
Hosseinimehr, SJ;Inanami, O;Kuwabara, M
我们研究了c-kit配体SCF对HL 60细胞放射敏感性的影响。X射线诱导HL 60细胞凋亡的SCF的存在下显着低于在SCF的情况下。SCF对X射线诱导的细胞凋亡的减弱作用可被ERK抑制剂PD 98059所消除，但不能被P13-K抑制剂wortmannin或PKC抑制剂GF 109203 X所消除。经X射线照射和SCF处理的细胞中磷酸化ERK 1/2（活性形式）和ERK 1/2调节的Survivin表达增加。然而，X射线照射单独诱导磷酸化ERK 1/2的表达下调。我们的研究结果表明，SCF激活c-kit通过上调ERK依赖的生存素在HL 60细胞中的表达而赋予辐射抗性。
We investigated the effect of SCF, a c-kit ligand, on the radiosensitivity of HL60 cells. X-ray-induced apoptosis in HL60 cells was significantly lower in the presence of SCF than in the absence of SCF. This attenuation of X-ray-induced apoptosis by SCF was abolished by PD98059 (an ERK inhibitor), but not by wortmannin (a P13-K inhibitor) or GF109203X (a PKC inhibitor). The expression of phospho-ERK1/2 (active form) and the ERK1/2-regulated expression of survivin were found to increase in cells treated with X irradiation and SCF. However, X irradiation alone induced down-regulation of the expression of phospho-ERK1/2. Our findings suggest that activation of c-kit by SCF confers radioresistance through up-regulation of ERK-dependent survivin expression in HL60 cells.