Activation of p65 NF-kappa B protein by p210(BCR-ABL) in myeloid cell line (p210(BCR-ABL) activates p65 NF-kappa B)
Activation of p65 NF-kappa B protein by p210(BCR-ABL) in myeloid cell line (p210(BCR-ABL) activates p65 NF-kappa B)
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DOI：
10.1038/sj.onc.1201411
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发表时间：
1997-11-06
期刊：
影响因子：
8
通讯作者：
DHalluin, JC
中科院分区：
文献类型：
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作者：
Hamdane, M;DavidCordonnier, MH;DHalluin, JC
嵌合酪氨酸激酶p210（BCR-ABL）参与慢性粒细胞白血病的发病机制。它在体外转化未成熟的造血细胞并消除IL-3依赖性生长。p210（BCR-ABL）介导其致癌性的机制尚未得到很好的阐明。识别嵌合蛋白靶向的转录因子可能有助于阐明这些机制。我们分析了p210（BCR-ABL）表达对DA 1细胞（一种IL-3依赖性鼠骨髓祖细胞系）中NF-κ B活性的影响。转录激活试验证明，激酶活性野生型p210（BCR-ABL）对NF-κ B活性具有特异性刺激作用。电泳迁移率超移分析表明，p65蛋白（RelA）DNA结合活性的存在下，在p210（BCR-ABL）转化的DA 1细胞，但不是在亲本DA 1细胞。在转化的DA 1细胞中RelA的活化可通过蛋白质稳定化而发生。使用RelA反义寡核苷酸的实验表明，p210（BCR-ABL）转染的细胞在去除IL-3后不能存活。此外，用p65反义寡核苷酸处理p210（BCR-ABL）转化的DA 1细胞后，细胞生长受到抑制。本研究提示，p65 NF-κ B B可能是p210（BCR-ABL）的效应子，并可能参与其诱导的转化过程。
The chimeric tyrosine kinase p210(BCR-ABL) is involved in the pathogenesis of chronic myelogenous leukemia. It transforms immature hematopoietic cells in vitro and abrogates IL-3-dependent growth. The mechanisms by which p210(BCR-ABL) mediates its oncogenicity are not well elucidated. Identifying transcription factors targeted by the chimeric protein may help to clarify these mechanisms. We have analysed the effect of p210(BCR-ABL) expression on NF-kappa B activity in DA1 cells (an IL-3-dependent murine myeloid progenitor cell line). A specific stimulation of NF-kappa B activity by kinase-active wild-type p210(BCR-ABL) has been evidenced by transcriptional activation assays. Electrophoretic mobility supershift assays revealed the presence of p65 protein (RelA) DNA binding activity in p210(BCR-ABL) transformed DA1 cells but not in parental DA1 cells. Activation of RelA in transformed DA1 cells may occur by protein stabilization. Experiments using oligonucleotides antisense to RelA showed that p210(BCR-ABL) transfected cells failed to survive after IL-3 removal. Moreover, inhibition of cellular growth was shown following treatment of p210(BCR-ABL) transformed DA1 cells by p65 antisense oligonucleotides. This study suggests that p65 NF-kappa B may be an effector for p210(BCR-ABL) and probably contributes to its induced transformation process.