PMID- 21475253
OWN - NLM
STAT- MEDLINE
DCOM- 20110916
LR  - 20211203
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Linking)
VI  - 25
IP  - 7
DP  - 2011 Jul
TI  - The serine/threonine kinase Pim-2 is a novel anti-apoptotic mediator in myeloma 
      cells.
PG  - 1182-8
LID - 10.1038/leu.2011.60 [doi]
AB  - 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, TNFalpha, 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-kappaB 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.
FAU - Asano, J
AU  - Asano J
AD  - Department of Medicine and Bioregulatory Sciences, University of Tokushima 
      Graduate School of Medicine, Tokushima, Japan.
FAU - Nakano, A
AU  - Nakano A
FAU - Oda, A
AU  - Oda A
FAU - Amou, H
AU  - Amou H
FAU - Hiasa, M
AU  - Hiasa M
FAU - Takeuchi, K
AU  - Takeuchi K
FAU - Miki, H
AU  - Miki H
FAU - Nakamura, S
AU  - Nakamura S
FAU - Harada, T
AU  - Harada T
FAU - Fujii, S
AU  - Fujii S
FAU - Kagawa, K
AU  - Kagawa K
FAU - Endo, I
AU  - Endo I
FAU - Yata, K
AU  - Yata K
FAU - Sakai, A
AU  - Sakai A
FAU - Ozaki, S
AU  - Ozaki S
FAU - Matsumoto, T
AU  - Matsumoto T
FAU - Abe, M
AU  - Abe M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110408
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Chromones)
RN  - 0 (EIF4EBP1 protein, human)
RN  - 0 (IL6 protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (MYC protein, human)
RN  - 0 (Morpholines)
RN  - 0 (Myeloid Cell Leukemia Sequence 1 Protein)
RN  - 0 (NF-kappa B)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (PIM2 protein, human)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Apoptosis/drug effects/*physiology
MH  - Apoptosis Regulatory Proteins/biosynthesis/genetics/*physiology
MH  - Cell Cycle Proteins
MH  - Cell Differentiation/drug effects
MH  - Cell Line
MH  - Chromones/pharmacology
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Interleukin-6/metabolism
MH  - Morpholines/pharmacology
MH  - Multiple Myeloma/*enzymology/pathology
MH  - Myeloid Cell Leukemia Sequence 1 Protein
MH  - NF-kappa B/metabolism
MH  - Neoplasm Proteins/biosynthesis/genetics/*physiology
MH  - Osteoclasts/drug effects/enzymology
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Processing, Post-Translational/drug effects
MH  - Protein Serine-Threonine Kinases/biosynthesis/genetics/*physiology
MH  - Proto-Oncogene Proteins/biosynthesis/genetics/*physiology
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Proto-Oncogene Proteins c-myc/metabolism
MH  - RNA Interference
MH  - RNA, Small Interfering/genetics/pharmacology
MH  - STAT3 Transcription Factor/metabolism
MH  - Signal Transduction/drug effects/physiology
MH  - Sirolimus/pharmacology
MH  - Stromal Cells/drug effects/enzymology
MH  - Transfection
MH  - Tumor Cells, Cultured/drug effects/metabolism
EDAT- 2011/04/09 06:00
MHDA- 2011/09/17 06:00
CRDT- 2011/04/09 06:00
PHST- 2011/04/09 06:00 [entrez]
PHST- 2011/04/09 06:00 [pubmed]
PHST- 2011/09/17 06:00 [medline]
AID - leu201160 [pii]
AID - 10.1038/leu.2011.60 [doi]
PST - ppublish
SO  - Leukemia. 2011 Jul;25(7):1182-8. doi: 10.1038/leu.2011.60. Epub 2011 Apr 8.