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ID 106134
Title Alternative
セリンスレオニンキナーゼPim-2は骨髄腫における新規抗アポトーシス媒介因子である
Pim-2 in myeloma cells
Author
Asano, Jin Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine
Nakano, Ayako University of Tokushima
Oda, Asuka University of Tokushima
Amou, Hiroe University of Tokushima
Takeuchi, Kyoko University of Tokushima
Yata, Kenichiro University of Tokushima
Sakai, Akira Hiroshima University
Ozaki, Shuji Tokushima University
Keywords
Pim-2
myeloma
bone marrow stromal cell
osteoclast
IL-6
Content Type
Thesis or Dissertation
Description
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-kB 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.
Journal Title
Leukemia
ISSN
08876924
14765551
NCID
AA10668706
AA12305962
Publisher
Springer nature
Volume
25
Issue
7
Start Page
1182
End Page
1188
Published Date
2011-04-08
Remark
内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨 : LID201405131005.pdf
論文本文 : LID201405231002.pdf
本論文は, 著者J Asanoの学位論文として提出され, 学位審査・授与の対象となっている。
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第2741号
Diploma Number
甲医第1202号
Granted Date
2014-03-19
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Oral Sciences
University Hospital
Medical Sciences
Institute of Advanced Medical Sciences