Document Detail

The serine/threonine kinase Pim-2 is a novel anti-apoptotic mediator in myeloma cells.
MedLine Citation:
PMID:  21475253     Owner:  NLM     Status:  MEDLINE    
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, TNFα, 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-κB 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.
J Asano; A Nakano; A Oda; H Amou; M Hiasa; K Takeuchi; H Miki; S Nakamura; T Harada; S Fujii; K Kagawa; I Endo; K Yata; A Sakai; S Ozaki; T Matsumoto; M Abe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-04-08
Journal Detail:
Title:  Leukemia     Volume:  25     ISSN:  1476-5551     ISO Abbreviation:  Leukemia     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-13     Completed Date:  2011-09-16     Revised Date:  2013-03-04    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  England    
Other Details:
Languages:  eng     Pagination:  1182-8     Citation Subset:  IM    
Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, Tokushima, Japan.
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MeSH Terms
Adaptor Proteins, Signal Transducing / metabolism
Apoptosis / drug effects,  physiology*
Apoptosis Regulatory Proteins / biosynthesis,  genetics,  physiology*
Cell Differentiation / drug effects
Cell Line
Chromones / pharmacology
Gene Expression Regulation, Neoplastic / drug effects
Interleukin-6 / metabolism
Morpholines / pharmacology
Multiple Myeloma / enzymology*,  pathology
NF-kappa B / metabolism
Neoplasm Proteins / biosynthesis,  genetics,  physiology*
Osteoclasts / drug effects,  enzymology
Phosphoproteins / metabolism
Phosphorylation / drug effects
Protein Processing, Post-Translational / drug effects
Protein-Serine-Threonine Kinases / biosynthesis,  genetics,  physiology*
Proto-Oncogene Proteins / biosynthesis,  genetics,  physiology*
Proto-Oncogene Proteins c-bcl-2 / metabolism
Proto-Oncogene Proteins c-myc / metabolism
RNA Interference
RNA, Small Interfering / genetics,  pharmacology
STAT3 Transcription Factor / metabolism
Signal Transduction / drug effects,  physiology
Sirolimus / pharmacology
Stromal Cells / drug effects,  enzymology
Tumor Cells, Cultured / drug effects,  metabolism
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Apoptosis Regulatory Proteins; 0/Chromones; 0/EIF4EBP1 protein, human; 0/IL6 protein, human; 0/Interleukin-6; 0/MYC protein, human; 0/Morpholines; 0/NF-kappa B; 0/Neoplasm Proteins; 0/PIM2 protein, human; 0/Phosphoproteins; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Proto-Oncogene Proteins c-myc; 0/RNA, Small Interfering; 0/STAT3 Transcription Factor; 0/STAT3 protein, human; 0/myeloid cell leukemia sequence 1 protein; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; 53123-88-9/Sirolimus; EC Kinases

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