The serine/threonine kinase Pim-2 is a novel anti-apoptotic mediator in myeloma cells

被引：98

作者：

Asano, J. ^{[1
]}

Nakano, A. ^{[1
]}

Oda, A. ^{[1
]}

Amou, H. ^{[1
]}

Hiasa, M. ^{[2
]}

Takeuchi, K. ^{[1
]}

Miki, H. ^{[1
]}

Nakamura, S. ^{[1
]}

Harada, T. ^{[1
]}

Fujii, S. ^{[1
]}

Kagawa, K. ^{[1
]}

Endo, I. ^{[1
]}

Yata, K. ^{[1
]}

Sakai, A. ^{[3
]}

Ozaki, S. ^{[4
]}

Matsumoto, T. ^{[1
]}

Abe, M. ^{[1
]}

机构：

[1] Univ Tokushima, Grad Sch Med, Dept Med & Bioregulatory Sci, Tokushima 7708503, Japan

[2] Univ Tokushima, Grad Sch Oral Sci, Dept Biomat & Bioengn, Tokushima 7708503, Japan

[3] Hiroshima Univ, Dept Hematol & Oncol, RIRBM, Hiroshima, Japan

[4] Tokushima Univ Hosp, Div Transfus Med, Tokushima, Japan

来源：

LEUKEMIA | 2011年 / 25卷 / 07期

关键词：

Pim-2; myeloma; bone marrow stromal cell; osteoclast; IL-6; MULTIPLE-MYELOMA; BONE DESTRUCTION; GROWTH-FACTOR; SURVIVAL; MICROENVIRONMENT; EXPRESSION; BAFF; INHIBITOR; RECEPTOR; CANCER;

D O I：

10.1038/leu.2011.60

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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

引用

页码：1182 / 1188

页数：7

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