Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells
Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells
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DOI：
10.1016/s1074-7613(00)80011-4
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发表时间：
1999-01-01
期刊：
影响因子：
32.4
通讯作者：
Jove, R
中科院分区：
文献类型：
--
作者：
Catlett-Falcone, R;Landowski, TH;Jove, R
白细胞介素6（IL-6）是骨髓瘤肿瘤细胞的主要存活因子，并通过STAT蛋白诱导信号传导。我们报道了STAT家族成员之一Stat 3在多发性骨髓瘤患者的骨髓单个核细胞和IL-6依赖的人骨髓瘤细胞系U266中被组成性激活。此外，U266细胞固有地抵抗Fas介导的凋亡，并表达高水平的抗凋亡蛋白Bcl-x（L）。阻断IL-6受体从Janus激酶到Stat 3蛋白的信号传导可抑制Bcl-x（L）表达并诱导凋亡，表明Stat 3信号传导对骨髓瘤肿瘤细胞的存活至关重要。这些发现提供了证据表明，组成性激活的Stat 3信号通路有助于通过阻止细胞凋亡的多发性骨髓瘤的发病机制。
Interleukin 6 (IL-6) is the major survival factor for myeloma tumor cells and induces signaling through the STAT proteins. We report that one STAT family member, Stat3 is constitutively activated in bone marrow mononuclear cells from patients with multiple myeloma and in the IL-6-dependent human myeloma cell line U266, Moreover, U266 cells are inherently resistant to Fas-mediated apoptosis and express high levels of the antiapoptotic protein Bcl-x(L). Blocking IL-6 receptor signaling from Janus kinases to the Stat3 protein inhibits Bcl-x(L) expression and induces apoptosis, demonstrating that Stat3 signaling is essential for the survival of myeloma tumor cells. These findings provide evidence that constitutively activated Stat3 signaling contributes to the pathogenesis of multiple myeloma by preventing apoptosis.