PMID- 10023775
OWN - NLM
STAT- MEDLINE
DCOM- 19990303
LR  - 20091119
IS  - 1074-7613 (Print)
IS  - 1074-7613 (Linking)
VI  - 10
IP  - 1
DP  - 1999 Jan
TI  - Constitutive activation of Stat3 signaling confers resistance to apoptosis in
      human U266 myeloma cells.
PG  - 105-15
AB  - Interleukin 6 (IL-6) is the major survival factor for myeloma tumor cells and
      induces signaling through the STAT proteins. We report that one STAT family
      member, Stat3, is constitutively activated in bone marrow mononuclear cells from 
      patients with multiple myeloma and in the IL-6-dependent human myeloma cell line 
      U266. Moreover, U266 cells are inherently resistant to Fas-mediated apoptosis and
      express high levels of the antiapoptotic protein Bcl-xL. Blocking IL-6 receptor
      signaling from Janus kinases to the Stat3 protein inhibits Bcl-xL expression and 
      induces apoptosis, demonstrating that Stat3 signaling is essential for the
      survival of myeloma tumor cells. These findings provide evidence that
      constitutively activated Stat3 signaling contributes to the pathogenesis of
      multiple myeloma by preventing apoptosis.
FAU - Catlett-Falcone, R
AU  - Catlett-Falcone R
AD  - H. Lee Moffitt Cancer Center and Research Institute, University of South Florida 
      College of Medicine, Tampa 33612, USA.
FAU - Landowski, T H
AU  - Landowski TH
FAU - Oshiro, M M
AU  - Oshiro MM
FAU - Turkson, J
AU  - Turkson J
FAU - Levitzki, A
AU  - Levitzki A
FAU - Savino, R
AU  - Savino R
FAU - Ciliberto, G
AU  - Ciliberto G
FAU - Moscinski, L
AU  - Moscinski L
FAU - Fernandez-Luna, J L
AU  - Fernandez-Luna JL
FAU - Nunez, G
AU  - Nunez G
FAU - Dalton, W S
AU  - Dalton WS
FAU - Jove, R
AU  - Jove R
LA  - eng
GR  - CA55652/CA/NCI NIH HHS/United States
GR  - CA77859/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Immunity
JT  - Immunity
JID - 9432918
RN  - 0 (Antineoplastic Agents)
RN  - 0 (BCL2L1 protein, human)
RN  - 0 (Bcl2l1 protein, mouse)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Receptors, Interleukin-6)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Trans-Activators)
RN  - 0 (Tyrphostins)
RN  - 0 (alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide)
RN  - 0 (bcl-X Protein)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis/drug effects/genetics/*immunology
MH  - DNA-Binding Proteins/*metabolism/physiology
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Immunity, Innate/drug effects
MH  - Mice
MH  - Multiple Myeloma/genetics/immunology/*metabolism/pathology
MH  - Promoter Regions, Genetic/drug effects
MH  - Protein-Tyrosine Kinases/physiology
MH  - Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors/biosynthesis
MH  - Receptors, Interleukin-6/physiology
MH  - STAT3 Transcription Factor
MH  - Signal Transduction/genetics/*immunology
MH  - Trans-Activators/*metabolism/physiology
MH  - Transcription, Genetic/drug effects
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - Tyrphostins/pharmacology
MH  - bcl-X Protein
EDAT- 1999/02/19 00:00
MHDA- 1999/02/19 00:01
CRDT- 1999/02/19 00:00
PHST- 1999/02/19 00:00 [pubmed]
PHST- 1999/02/19 00:01 [medline]
PHST- 1999/02/19 00:00 [entrez]
AID - S1074-7613(00)80011-4 [pii]
PST - ppublish
SO  - Immunity. 1999 Jan;10(1):105-15.