The serine/threonine kinase Pim-2 is a novel anti-apoptotic mediator in myeloma cells
The serine/threonine kinase Pim-2 is a novel anti-apoptotic mediator in myeloma cells
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DOI：
10.1038/leu.2011.60
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发表时间：
2011-07-01
期刊：
影响因子：
11.4
通讯作者：
Abe, M.
中科院分区：
文献类型：
--
作者：
Asano, J.;Nakano, A.;Abe, M.
骨髓基质细胞（BMSCs）和破骨细胞（OCs）通过复杂的因子赋予多发性骨髓瘤（MM）细胞存活。我们在此证明IL-6和TNF家族细胞因子，TNF α， BAFF和APRIL，而不是IGF-1共同增强MM细胞中丝氨酸/苏氨酸激酶Pim-2的表达。BMSCs和OCs分别通过IL-6/STAT3和NF-kappa B途径上调MM细胞中Pim-2的表达。Pim-2短干扰RNA降低骨髓间充质干细胞或细胞间充质干细胞共培养的MM细胞活力。因此，上调Pim-2似乎是MM细胞存活的一种新的抗凋亡机制。有趣的是，雷帕霉素抑制剂的哺乳动物靶点雷帕霉素与Pim-2沉默联合进一步抑制MM细胞活力。PI3K抑制剂(Z)-5-（4-丙氧基苄基）噻唑烷- 2,4 -二酮和PI3K抑制剂LY294002共同促进MM细胞死亡。Pim抑制剂抑制4E-BP1磷酸化，同时降低Mcl-1和c-Myc。因此，Pim-2可能成为MM治疗的新靶点。白血病（2011）25,1182-1188；doi: 10.1038 / leu.2011.60;2011年4月8日在线发布
Bone marrow stromal cells (BMSCs) and osteoclasts (OCs) confer multiple myeloma (MM) cell survival through elaborating factors. We demonstrate herein that IL-6 and TNF family cytokines, TNF alpha, BAFF and APRIL, but not IGF-1 cooperatively enhance the expression of the serine/threonine kinase Pim-2 in MM cells. BMSCs and OCs upregulate Pim-2 expression in MM cells largely via the IL-6/STAT3 and NF-kappa B pathway, respectively. Pim-2 short interfering RNA reduces MM cell viability in cocultures with BMSCs or OCs. Thus, upregulation of Pim-2 appears to be a novel anti-apoptotic mechanism for MM cell survival. Interestingly, the mammalian target of rapamycin inhibitor rapamycin further suppresses the MM cell viability in combination with the Pim-2 silencing. The Pim inhibitor (Z)-5-(4-propoxybenzylidene) thiazolidine-2, 4-dione and the PI3K inhibitor LY294002 cooperatively enhance MM cell death. The Pim inhibitor suppresses 4E-BP1 phosphorylation along with the reduction of Mcl-1 and c-Myc. Pim-2 may therefore become a new target for MM treatment. Leukemia (2011) 25, 1182-1188; doi:10.1038/leu.2011.60; published online 8 April 2011