Effects of a non-IGF binding mutant of IGFBP-5 on cell death in human breast cancer cells
Effects of a non-IGF binding mutant of IGFBP-5 on cell death in human breast cancer cells
复制标题
DOI：
10.1016/s0006-291x(02)00570-3
复制
发表时间：
2002-06-28
影响因子：
3.1
通讯作者：
Holly, JMP
中科院分区：
文献类型：
--
作者：
Perks, CM;McCaig, C;Holly, JMP
我们之前已经证明，IGFBP-5单独对细胞死亡没有影响，但可以调节神经酰胺诱导的Hs578T IGF无反应细胞的凋亡。为了研究IGFBP-5是否维持其调节igf应答细胞凋亡的内在能力，我们使用了IGFBP-5的非igf结合突变体。在Hs578T细胞中，未糖基化、糖基化或突变的IGFBP-5单独对细胞死亡均无影响，而所有形式的IGFBP-5均抑制神经酰胺诱导的细胞凋亡。在对igf有反应的MCF-7细胞中，每种野生型都能减少神经酰胺诱导的细胞死亡，但突变型IGFBP-5没有影响。然而，在突变型IGFBP-5存在的情况下，IGF-I不再赋予存活，在野生型IGFBP-5存在的情况下，长R3 IGF-I也无法赋予存活。综上所述，所有形式的IGFBP-5调节神经酰胺诱导的Hs578T细胞凋亡。在MCF-7细胞中，IGFBP-5可以促进igf - 1诱导的存活，但如果阻止IGFBP-5与IGFBP-5的关联，IGFBP-5也会阻断igf - 1诱导的存活。(C) 2002 Elsevier Science （USA）。版权所有。
We have demonstrated previously that IGFBP-5 alone had no effect on cell death but modulated ceramide-induced apoptosis in Hs578T IGF non-responsive cells. To investigate if IGFBP-5 maintains its intrinsic ability to modulate apoptosis in IGF-responsive cells, we used a non-IGF binding mutant of IGFBP-5. In Hs578T cells, non-glycosylated, glycosylated or mutant IGFBP-5 alone each had no effect on cell death, whereas all forms inhibited ceramide-induced apoptosis. In IGF-responsive MCF-7 cells, each wild type form reduced ceramide-induced cell death but mutant IGFBP-5 was without effect. In the presence of mutant IGFBP-5, however, IGF-I no longer conferred survival and in the presence of wild type IGFBP-5, long R3 IGF-I was also unable to confer survival. In summary, all forms of IGFBP-5 modulated ceramide-induced apoptosis in Hs578T cells. In MCF-7 cells, IGF-I-induced survival could be facilitated by IGFBP-5, but also blocked by IGFBP-5 if association with IGFBP-5 was prevented. (C) 2002 Elsevier Science (USA). All rights reserved.