Aurora kinase A critically contributes to the resistance to anti‐cancer drug cisplatin in JAK2 V617F mutant‐induced transformed cells
Aurora kinase A critically contributes to the resistance to anti‐cancer drug cisplatin in JAK2 V617F mutant‐induced transformed cells
复制标题
DOI：
10.1016/j.febslet.2011.04.068
复制
发表时间：
2011-06
期刊：
影响因子：
3.5
通讯作者：
K. Sumi;K. Tago;T. Kasahara;M. Funakoshi-Tago
中科院分区：
文献类型：
--
作者：
K. Sumi;K. Tago;T. Kasahara;M. Funakoshi-Tago
JAK2 V617F突变体通过异常激活多种转录因子诱导转化。我们发现突变体JAK2通过表达c-Myc显著诱导极光激酶A （Aurka）的表达。有趣的是，JAK2突变体增强了对顺铂（CDDP）诱导的DNA损伤的耐药性，并有效抑制了细胞凋亡。Ba/F3细胞中Aurka的异位表达对CDDP表现出类似的抗性，这需要激酶活性。相反，在表达JAK2突变体的细胞中敲低和抑制Aurka可消除对CDDP的抗性。综上所述，Aurka很可能对JAK2 V617F突变体转化的细胞抵抗DNA损伤至关重要。
JAK2 V617F mutant induces transformation through aberrant activation of various transcription factors. We found that the expression of Aurora kinase A (Aurka) was significantly induced by mutant JAK2 through c-Myc expression. Interestingly, mutant JAK2 enhanced resistance to cisplatin (CDDP)-induced DNA damage, and effectively suppressed apoptosis. Ectopic expression of Aurka in Ba/F3 cells exhibited similar resistance to CDDP, and this required kinase activity. Conversely, knockdown and inhibition of Aurka in cells expressing mutant JAK2 abolished the resistance to CDDP. Taken together, Aurka is most likely critical for resistance to DNA damage in cells transformed by JAK2 V617F mutant.