PMID- 20228272
OWN - NLM
STAT- MEDLINE
DCOM- 20100525
LR  - 20211203
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 115
IP  - 18
DP  - 2010 May 6
TI  - A proto-oncogene BCL6 is up-regulated in the bone marrow microenvironment in 
      multiple myeloma cells.
PG  - 3772-5
LID - 10.1182/blood-2010-02-270082 [doi]
AB  - Constitutive B-cell lymphoma 6 (Bcl-6) expression was undetectable in multiple 
      myeloma (MM) cell lines, except U266 cells. However, it was up-regulated by 
      coculture with bone marrow (BM) stromal cell-culture supernatant (SCCS). Bcl-6 
      expression in patient MM cells in the BM was positive. Anti-interleukin-6 
      (IL-6)-neutralizing antibody significantly blocked SCCS-induced Bcl-6 in MM 
      cells. Indeed, IL-6 strongly triggered Bcl-6 expression in MM cells, whereas 
      Janus kinase inhibitor and STAT3 siRNA down-regulated Bcl-6. Tumor necrosis 
      factor-alpha (TNF-alpha) also triggered Bcl-6, but independently of STAT3, 
      whereas IkappaB kinasebeta inhibitor down-regulated TNF-alpha-induced Bcl-6, 
      indicating that the canonical nuclear factor-kappaB pathway mediates 
      TNF-alpha-induced Bcl-6 expression. Importantly, down-regulation of Bcl-6 by 
      shRNA significantly inhibited MM cell growth in the presence of SCCS. Our results 
      therefore suggest that Bcl-6 expression in MM cells is modulated, at least in 
      part, via Janus kinase/STAT3 and canonical nuclear factor-kappaB pathways and 
      that targeting Bcl-6, either directly or via these cascades, inhibits MM cell 
      growth in the BM milieu.
FAU - Hideshima, Teru
AU  - Hideshima T
AD  - Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer 
      Institute, Boston, MA 02115, USA.
FAU - Mitsiades, Constantine
AU  - Mitsiades C
FAU - Ikeda, Hiroshi
AU  - Ikeda H
FAU - Chauhan, Dharminder
AU  - Chauhan D
FAU - Raje, Noopur
AU  - Raje N
FAU - Gorgun, Gullu
AU  - Gorgun G
FAU - Hideshima, Hiromasa
AU  - Hideshima H
FAU - Munshi, Nikhil C
AU  - Munshi NC
FAU - Richardson, Paul G
AU  - Richardson PG
FAU - Carrasco, Daniel R
AU  - Carrasco DR
FAU - Anderson, Kenneth C
AU  - Anderson KC
LA  - eng
GR  - R0-1 CA50947/CA/NCI NIH HHS/United States
GR  - P0-1 78378/PHS HHS/United States
GR  - P01 CA078378/CA/NCI NIH HHS/United States
GR  - P01 CA155258/CA/NCI NIH HHS/United States
GR  - R01 CA050947/CA/NCI NIH HHS/United States
GR  - R01 CA124929/CA/NCI NIH HHS/United States
GR  - P50 CA100707/CA/NCI NIH HHS/United States
GR  - CA10070/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100312
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (BCL6 protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Interleukin-6)
RN  - 0 (MAS1 protein, human)
RN  - 0 (NF-kappa B)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (Proto-Oncogene Proteins c-bcl-6)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (STAT3 Transcription Factor)
RN  - EC 2.7.10.2 (Janus Kinases)
SB  - IM
MH  - Antibodies, Neutralizing/pharmacology
MH  - Blotting, Western
MH  - Bone Marrow/*metabolism
MH  - Bone Marrow Cells/*metabolism
MH  - Cell Proliferation
MH  - DNA-Binding Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - Humans
MH  - Interleukin-6/pharmacology
MH  - Janus Kinases/genetics/metabolism
MH  - Multiple Myeloma/*metabolism/pathology
MH  - NF-kappa B/genetics/metabolism
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogene Proteins c-bcl-6
MH  - RNA, Messenger/genetics/metabolism
MH  - RNA, Small Interfering/pharmacology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - STAT3 Transcription Factor/genetics/metabolism
MH  - Signal Transduction
MH  - Tumor Cells, Cultured
MH  - Up-Regulation
PMC - PMC2865869
EDAT- 2010/03/17 06:00
MHDA- 2010/05/26 06:00
PMCR- 2011/05/06
CRDT- 2010/03/16 06:00
PHST- 2010/03/16 06:00 [entrez]
PHST- 2010/03/17 06:00 [pubmed]
PHST- 2010/05/26 06:00 [medline]
PHST- 2011/05/06 00:00 [pmc-release]
AID - S0006-4971(20)35064-3 [pii]
AID - 2010/270082 [pii]
AID - 10.1182/blood-2010-02-270082 [doi]
PST - ppublish
SO  - Blood. 2010 May 6;115(18):3772-5. doi: 10.1182/blood-2010-02-270082. Epub 2010 
      Mar 12.