FLIP is Constitutively Hyperexpressed in Fas-resistant U266 Myeloma Cells, but Is Not Induced by IL-6 in Fas-sensitive RPMI8226 Cells
FLIP is Constitutively Hyperexpressed in Fas-resistant U266 Myeloma Cells, but Is Not Induced by IL-6 in Fas-sensitive RPMI8226 Cells
复制标题
FLIP 在 Fas 耐药性 U266 骨髓瘤细胞中持续高表达，但在 Fas 敏感型 RPMI8226 细胞中不受 IL-6 诱导
DOI：
10.1007/s10059-000-0552-0
复制
发表时间：
2000
影响因子：
3.8
通讯作者：
H. Um
中科院分区：
文献类型：
--
作者：
Do Kyun Kim;E. S. Cho;Joo;H. Um
尽管Fas的表达，骨髓瘤细胞的一些克隆是抵抗Fas介导的凋亡。为了确定参与耐药性的细胞因子，我们使用骨髓瘤细胞RPMI 8226和U266的两个克隆进行了比较研究。据报道，这些细胞以相似的水平表达细胞表面Fas，但只有RPMI 8226细胞在抗Fas处理后失去活力。U266细胞对抗Fas的抗性似乎并不反映Bcl-2、Bcl-XL和Bax的失调，因为这些蛋白质在RPMI 8226和U266细胞中以相似的水平表达。此外，用IL-6处理RPMI 8226细胞并没有显著改变这些蛋白质的水平，IL-6是一种抑制Fas介导的RPMI 8226细胞死亡的细胞因子。有趣的是，在U266细胞中，内源性Fas信号抑制剂FLIPL的mRNA水平组成性升高。与该观察结果一致，U266细胞表达FLIPL蛋白及其截短的43 kDa产物，这在FLIPL过表达细胞中可见。在RPMI 8226中未检测到FLIPL蛋白的截短形式。此外，U266细胞中截短的FLIPL的水平显著高于RPMI 8226中的pro-FLIPL的水平。总体数据表明，FLIPL在U266细胞中组成性高表达。然而，IL-6未能增强任一测试细胞中FLIP分子的蛋白水平。因此，FLIPL似乎在U266细胞对Fas凋亡作用的内在抗性中起作用，但不参与IL-6的保护作用。
Despite the expression of Fas, some clones of myeloma cells are resistant to Fas-mediated apoptosis. To define a cellular factor involved in the resistance, we performed a comparative study using two clones of myeloma cells, RPMI8226 and U266. These cells were reported to express cell surface Fas at similar levels, but only RPMI8226 cells lost their viability upon anti-Fas treatment. The resistance of U266 cells to anti-Fas did not appear to reflect dysregulation of Bcl-2, Bcl-XL, and Bax, because these proteins were expressed in both RPMI8226 and U266 cells to similar levels. Moreover, levels of those proteins were not significantly altered by treating RPMI8226 cells with IL-6, a cytokine which suppresses the Fas-mediated death of RPMI8226 cells. Interestingly, mRNA levels of FLIPL, an endogenous inhibitor of Fas signaling, were constitutively elevated in U266 cells. Consistent with this observation, U266 cells expressed both FLIPL protein and its truncated 43 kDa product which is seen in FLIPL-overexpressing cells. The truncated form of FLIPL protein was not detected in RPMI8226. Moreover, the levels of truncated FLIPL in U266 cells were considerably higher than those of pro-FLIPL in RPMI8226. The overall data indicate that FLIPL is constitutively hyperexpressed in U266 cells. However, IL-6 failed to enhance the protein levels of FLIP molecules in either of the tested cells. It appears, therefore, that FLIPL plays a role in the intrinsic resistance of U266 cells to the apoptotic action of Fas, but is not involved in the protective action of IL-6.
影响因子：
20.3
作者：
Chauhan, D;Kharbanda, S;Anderson, KC
通讯作者：
Anderson, KC